Biochemistry - Test II

How does folding cause long range interactions?

-1/4 to 1/3 of all amino acids are involved in bends -β bends are the result of proline and glycine -turn promoting amino acids are threonine and serine

Collagen structure

-3 left-handed helices twist around each other to form a right-handed super helix (provides enormous tensile strength with no capacity to stretch, can support up to 10,000 times their own weight -collagen fibrils aligned in staggered fashion with inter-helices covalent bonds present

What are the characteristics of silk fibroin?

-A type of fibrous protein that consists of stack anti-parallel beta strands stabilized by hydrogen bonding and many - many gly and ala -strong -flexible -no stretching

What are some unique features of proteins?

-Dynamic; function depends on interactions with other term-84molecules -Proteins are flexible. Binding can cause induced fit -Regulated by other ligands

In considering higher levels of protein structure (e.g. tertiary and quaternary structures), what are the two categories we have to classify them?

-Fibrous -Globular

What is activation energy needed for?

-Offset entropy reduction -Desolvation -Distortion of substrate -Positioning of catalytic groups

What are factors that affect the binding of O2 (T <-> R)?

-PO2 in environment -pH

Why can't protein folding be random?

-There are so many possible conformations that it would take 10⁷⁷ years to get the right fold if it was possible to be random -for example, e. coli: 100 aa takes 5 seconds to make including folding (so we know there are shortcuts)

What stabilizes an α helix

-amino acids with oppositely charged R groups 3-4 amino acids away -amino acids with hydrophobic R groups 3-4 amino acids away

Properties of Enzymes

-catalytic power -high degree of specificity -function in aqueous solutions with mild conditions of temperature and pH (usually) -typically proteins -have a MW of 12,000 or higher -must maintain native structures to be functional -some require cofactors

Catalytic Functional Groups aid in what?

-cleavage and formation of bonds -group transfer to or from a substrate

Collagen specific characteristics

-evolved for strength -found in connective tissues (tendons, cartilage, organic matrix of bones, cornea of the eye) -left-handed α-helix with 3 aa per turn and repeating tripeptide sequence of Gly-X-Y - 35% Gly, 21% Pro/hydroxypro, and 11% Ala

α-keratin specific characteristics

-evolved for strength -only found in mammals -type of intermediate filament -right handed α-helix -strength is amplified by two coiled chains that will wind around each other (left-handed supertwist with tight packing of hydrophobic aa residues -coiled coils form larger, higher order structures: protofilaments and protofibrils

List the characteristics of α-keratin and collagen

-give strength -insoluble in water because the hydrophobic residues are on the outside

Factors that can cause denaturation

-heat (disrupts H bonds) -organic solvents (disrupts the hydrophobic core of globular proteins) -extremes in pH (alters the net charge of the protein)

Why does denaturation of protein due to heat an pH usually lead to precipitation in aqueous solvents?

-hydrophobic residues are exposed -since this is an aqueous environment, the denatured proteins will associate and form a precipitation

Why do proteins that have been denatured due to heat and pH precipitate in aqueous solvents?

-hydrophobic residues exposed -aqueous environment causes the denatured proteins to associate and form precipitate

Native form

-most thermodynamically stable -protein is folded and functional -non-covalent forces (sometimes disulfide bonds)

Pathways that contribute to proteostasis

-nascent polypeptides - intermediate - native protein (Direct) - nascent polypeptides - intermediate - misfolded - degraded (proteosome) -nascent polypeptides - intermediate - misfolded - aggregate - degraded (autophagy, lysosome involvement) NOTE: sometimes misfolded proteins/aggregates can be converted back into intermediates

The secondary structure a protein takes depends on:

-non-covalent interactions -types of amino acids

β turn (type I)

-occurs where a polypeptide chain abruptly reverses direction (180 degrees) -4 amino acids -Hydrogen bond between aa 1 and 4 (backbone) -glycine and proline are common

Why does α helix form?

-optimum use of hydrogen bonding -the types of amino acids (see the card 7 and 8)

What happens to the pH and oxygen affinity back in the lungs?

-pH rises (7.2->7.6) -His group deprotonated (NOT all or none) -His-Asp bond lost, less stable -Promotes R state -incr. PO2

3 types of bonds that make up the peptide bond

-peptide bond -N-C α bond (angle called phi Φ) -Cα-C bond (angle called psi ψ)

Fibrous Protein characteristics

-polypeptide chains in a long strands/sheets -single type of 2⁰ structure -structural roles

helical structure characteristics

-r groups point out -planes of rigid peptide bond are parallel to long axis -3.6 aa per helical turn -0.54 nm per helical turn -usually is right handed

Globular Protein characteristics

-spherical/globular shape -might have more than 1 type of 2⁰ structure -most non-structural proteins (eg enzymes)

which types of aa help to destabilize alpha helix

-string of aa with like charged R groups -string of aa with bulky R groups (steric hindrance) -proline, because phi bond is part of rigid ring in this and N has no H to participate in h bonding -glycine string, because it is so flexible that it forms too tight of a coil

What destabilizes an α helix

-string of amino acids with like-charged R groups -string of amino acids with bulky R groups -Two important amino acids: proline or a sting of glycines

ΔG⁰ (KJ/mol)ᵃ

-the propensity of amino acid residues to take up an α helical conformation -the difference in free-energy change relative to alanine required for an amino acid residue to take up the α helical conformation

Tertiary structure

-the spatial arrangement between ALL amino acids -can contain one or more secondary structures -can be determined by long range interactions (See card 14)

Characteristics of an α helix conformation

-tightly wound around a vertical axis -R groups pointing out -planes of rigid peptide bond are parallel to the long axis -3.6 amino acid/helical turn -0.54 nm/helical turn -usually right-handed

sequence of a polypeptide chain

-type and order of sequence ​

What is the tripeptide Gly-X-Y sequence in collagen

-x is usually proline -y is usually hydroxyproline NOTE: these maintain the stability of collagen

β conformation characteristics

-zig-zag -amino acids found in the middle of the chain: phenylalanine, tyrosine, tryptophan, isoleucine, threonine, and valine -β pleated sheet is parallel and antiparallel -sheets can stack

list some examples of fibrous proteins mentioned in lecture

-α-keratin -collagen -silk fibroin

rate constant/proportionality constant of the following translates to what k = 0.03 k= 1.00 k = 5.00

1) 3% of S (substrate) is converted to P (products) in one second 2) 100% of S is converted to P in one second 3) the conversion of S to P occurs in a faction of a second it is so fast.

What is the symbol free energy? What is the symbol for standard free energy? What is the symbol for biochemical standard free energy? What is the symbol for the change in energy needed to reach the transition state. In other words, the activation energy symbol?

1) G 2) G° 3) G'° 4) ∆Gŧ

Disulfide bonds are typically seen in globular proteins that are...?

1) Secreted proteins that go to a rough environment. They keep the protein stable in harsh parts of the body. 2) small proteins that can't form as many non-covalent bonds and need disulfide bonds to stabilize them

Which protein is responsible for forming amyloids in type-II diabetes? What cells secrete this protein?

1) amyloid polypeptide (IAPP) , [also called amylin] 2) ß-cells

What protein is responsible for forming amyloids in Alzheimer's disease? Where does it come from?

1) amyloid-ß peptide 2) The amyloid-ß peptide is actually supposed to contain two α-helices and is part of a larger transmembrane protein called amyloid-ß precursor protein in human tissues. When cleaved from the transmembrane protein, the α-helices are unstable and are reformed into the amyloid-ß peptide which forms amyloids in the extracellular regions around neurons. **as an aside intracellular accumulation of tau protein aggregates also occurs in Alzheimer's, but this may not be as important to know.

Describe the steps of protein folding with chaperonin.

1) an unfolded or misfolded polypeptide is placed in an empty trans camber of the the GroEL of the chaperonin. 2) a cap of the GroES of the chaperonin locks the unfolded/misfolded polypeptide inside the chaperonin. 3) the chamber will restrict the number of protein conformations that can occur and allow for a controlled and quick folding. During this time 7 ATPs on the outside of the chaperone are hydrolized. 4) cap is released and protein comes out as a either an intermediate or completely folded. 5) if the protein released is not folded correctly, it will enter the other chamber of the chaperonin. 6) if the protein released is folded correctly, a new protein can enter the opposite chamber to be folded.

In a Chaperonin, the chamber that has a currently folding protein is called the ... chamber while the empty chamber is called the ... chamber.

1) cis 2) trans

Native proteins are held together by many types of (covalent/non-covalent) bonds and sometimes held together by ... bonds. Of the bonds involved, which is/are missing from this list below? 1) hydrogen bonding 2) ionic

1) covalent 2) disulfide 3) van der Waals and hydrophobic interactions

Up to 18% of α-keratin contains this type of amino acid....which allows a particular type of covalent bond called... This is plays a role in the stabilization for coiled coils, protofilaments, and protofibrils to stick together.

1) cysteine 2) disulfide bonds

What is the protein that is responsible for cystic fibrosis? What does it do, and what happens to it in cystic fibrosis that prevents its proper function?

1) cystic fibrosis transmembrane conductance regulator (CFTR) 2) It is an ion channel for Cl- export. Cl- export allows water to be released with mucus from epithelial cells. 3) Misfolding of the CFTR occurs when a single Phe residue is deleted. Without Cl- export, less water is released from the mucus epithelial cells produce. Cells cannot protect from bacterial infections that damage the lungs, reduce respiration efficiency, and lead to shortened life-span.

The overall amino acid composition of collagen is 35% ..., 21%..., and .11%... Why is it that we see this particular pattern?

1) gly - is small and is usually located in the middle of collagen to allow for tight coiling 2) pro/hydroxyproline - maintain stability of the collagen molecule 3) ala - also a small R group that allows for tight coiling

What intramolecular interactions hold globular proteins together?

1) hydrophobic interactions - the hydrophobic parts of the protein collect together in the inside 2) hydrophilic interactions- the polar and ionic amino acids in the protein are positioned on the surface of the globular protein 3) occasional disulfide bonds

Vitamin C (ascorbic acid) plays a critical role in ensuring that proline is converted to ... at exactly the the Y position in the Gly-X-Y tripeptide pattern in collagen. It is critical the proline is modified so that it is pointing in the ... conformation so that collagen helices can form properly. Without proper collagen formation due to lack of vitamin C, a person can develop a disease called ... which envelops a whole range of symptoms such as tooth loss, bone pain, fatigue, hear failure, and small hemorrhages can occur.

1) hydroxyproline 2) Cγ-exo 3) scurvy

Vitamin C plays a/an ..(1).. role in the biochemical processes that ensure proline is modified for proper collagen formation. The enzyme ... is responsible for modifying proline into ..(2).. This enzyme can't do its job with proline when its ..(3).. is has been oxidized by interactions with α-ketoglutarate. So, vitamin C's job is to ..(4). this enzyme to restore its proper function. That way our bodies can continue to produce plenty of collagen fibers and avoid the disease of ..(5)..

1) indirect 2) prolyl 4-hydroxylase 3) hydroxyproline 4) heme iron (Fe2+) 5) oxidize 6) scurvey

What makes α-keratin so unusually strong?

1) it has two chains that form a left handed twisted coil (essentially a coiled coil) 2) α-keratin posses many hydrophobic residues that causes the protein and coils to tightly pack together

Describe the structure of a chaperonin.

1) it has two chambers called GroEL 2) it has two caps called GroES 2) each chamber is made of 7 subunits and likewise, the cap is made of 7 subunits

what does the unfolded protein response (UPR) do?

1) it signals for the decease of protein synthesis to give chaperons more time to fold proteins and attend to misfolded and denatured proteins and aggregates 2) it signals for an increase in chaperons to again attend to the formation of aggregates and take care of high levels of denatured or misfolded proteins.

PrPc is the ... protein in brain cells while ... is the abnormal prion in scrappie. The abnormal conformation is different how?

1) normal 2) PrPsc 3) the abnormal conformation has converted α-helicies to ß-sheets that expose more hydrophobic residues that encourage aggregations to form.

...plays the largest role in restricting rotation around the polypeptide bond, and ... plays the largest role in determining and stabilizing native protein structure.

1) partial double bond character of the peptide bond 2) H-bonding

The heme group in myoglobin contains has two components, a ... and a ... atom.

1) protoporphyrin ring 2) iron

What are the three possible options that can occur when a protein has been denatured?

1) renaturation (rare and only occurs in small proteins) 2) ubiquitin-proteasome system which degrades the denatured protein 3) aggregation of proteins and autophagy of aggregates and their destruction by lysosomes

What are the two methods used for protein folding? Which method is more common?

1) spontaneous folding 2) chaperone assistance (more common)

Collagen fibrils align in a ... fashion to produce a higher order structure. These structures are held together by ... bonds between the collagen fibrils. This unique type of bond occurs between two modified ... residues (now called ... residues) of two different collagen fibrils.

1) staggered 2) dehydro hydroxy lysino norleucine bonds 3) lysine 4) norleucine

What are two ways to classify enzymes?

1) systematic name that reflects or identifies the name of the reaction the enzyme catalyzes 2) the 4 digit classification system

Water stabilizes substrate. Why does it tend to bind enzyme?

1)Increase in entropy of water molecules (previously discussed) 2)Binding energy from non-covalent bonds that form

Enzyme classification

1. Systematic name 2. Four digit classification number

Three mechanisms for transient covalent bonds/group transfers between E and S

1. general acid-base catalysis 2. covalent catalysis 3. metal catalysis

Stepwise process of spontaneous protein folding

1. secondary structures form 2. formation of motifs (interactions between secondary structures) 3. Protein completely folded (hydrophobic interactions play a major role) 4. most thermodynamically stable conformation (lowest free energy) is formed

By not being able to rotate around the peptide bond, peptides are limited in the number of conformations by ...

1/3

Molecular weight of enzymes

12,000 to over 1 million

what degree turn is present in antiparallel beta plated sheets?

180 degree

which position is proline at in beta turn 1

2, because it can be present in either the trans (creating linear) or cis (creating cyclical structure) form the cis form changes the direction of the polypeptide chain and the trans form maintains the direction of the polypeptide

Despite the fact that chaperones are present, ... or more of all proteins still end up misfolding.

25%

Chymotrypsin mw

25,000

How many amino acid residues do myoglobin, hemoglobin, neuroglobin, and cytoglobin have in common?

27

which position is glycine at in beta turn 1?

3, because there will be very little steric hindrance

What is the globin protein composed of?

4 polypeptide chains; 2 alpha chains and 2 beta chains. Each chain has a heme group.

The Protein Data bank (PDB), contains over 100,000 proteins that are sorted into what four classes based on the motif structures present in the proteins. How are databases such as the PDB useful for the study of evolution?

A) the four classes are 1) all α-helices in the motif, 2) all ß-sheets in the motif, 3) α/ß category where α and ß segments are interspersed 4) α + ß category where α and ß segments are somewhat segregated. In other words you have long spans of α and then long spans of ß segments in the motif. B) Motifs can be preserved over evolutionary time even if the amino acid sequence may change slightly. The more similar the motif, the more closely two species are related on a phylogenetic tree.

ATP + Glucose --> ?? Name the enzyme that catalyzes this reaction.

ADP + Glucose-6-Phosphate the enzyme that catalyzes this reaction is glucose phosphotransferase

enzyme for catalyzes attaching phosphate to ATP+Glucose

ATP:Glucose phosphotransferase

Where are the His residues on the chains?

All chains have His residue on E and F helices

The native form of a protein is best described as (circle all that apply): a. fully folded and functional b. most thermodynamically stable c. held together by covalent bonds d. held together by non-covalent bonds

All except c. are correct.

What interaction stabilizes the T state?

Alpha chain lysine and B chain terminal histidine (ionic) Alpha chain carboxyl (-) and Beta chain amino (+)

What are the sizes of the alpha and beta chains?

Alpha: 141 aa Beta: 146 aa

flavin adenine dinucleotide (FAD)

An energy carrier that accepts electrons and feeds them into the electron transport chain

What causes altitude sickness?

At high altitude, the pressure of oxygen is lower, so the RBCs pick up less oxygen in the lungs because not enough hemoglobins are in the T state for the lower oxygen pressure to be absorbed efficiently

[The unfolding of the α helix of a polypeptide to a randomly coiled conformation is accompanied by a large decrease in a property called specific rotation, a measure of a solution's capacity to rotate circularly polarized light. Polyglutamate, a polypeptide made up of only L-Glu residues, has the α helix conformation at pH 3. When the pH is raised to 7, there is a large decrease in the specific rotation of the solution. Similarly, polylysine (L-lys residues) is an α helix at pH 10, but when the pH is lowered to 7, the specific rotation also decreases.] What is the explanation for the effect of the pH changes on the conformations of polyGlu and polyLys? Why does the transition occur over such a narrow range of pH?

At pH>6, the carboxyl groups of poly Glu are deprotonated; repulsion among negatively charged carboxylate groups leads to unfolding. Similarly, at pH 7, the amino groups of poly Lys are protonated; repulsion among these positively charged groups also leads to unfolding.

How does BPG help high altitude sickness?

Binding BPG promotes the T state, which reduces the amount of oxygen picked up in the lungs to 86% saturated, but increases the oxygen released to tissues (49% saturated)

What is positive cooperative binding?

Binding of one ligand to one subunit causes a change in conformation to other subunits which facilitates the binding of ligands to other subunits Also works to help unbind ligands

CH5B

CH5B

Ch 4A

Ch 4A

Ch 4C

Ch 4C

Ch 4D

Ch 4D

Ch 4E

Ch 4E

Ch 4B

Ch4B

Ch4F

Ch4F

Ch4G

Ch4G

Ch5A

Ch5A

Ch5B

Ch5B

Ch5C

Ch5C

Ch5D

Ch5D

Ch6C

Ch6

Ch6A

Ch6A

Ch6B

Ch6B

lyase 4

Cleavage of C-C, C-O, C-N, or other bonds by elimination, leaving double bonds or rings, or addition of groups to double bonds ​

Emil Fischer's lock and key model

Complementary in size, shape and non-covalent interactions R groups of substrate residues interact with R groups of active site residues

[Some natural proteins are rich in disulfide bonds, and their mechanical properties (tensile strength, viscosity, hardness, etc.) are correlated with the degree of disulfide bonding.] Most globular proteins are denatured and lose their activity when briefly heated to 65C. However, globular proteins that contain multiple disulfide bonds often must be heated longer at higher temperatures to denature them. One such protein is bovine pancreatic trypsin inhibitor (BPTI), which has 58 amino acid residues in a single chain and contains three disulfide bonds. On cooling a solution of denatured BPTI, the activity of the protein is restored. What is the molecular basis for this property?

Cystine residues (disulfide bonds) prevent the complete unfolding of the protein.

Which of the following is true regarding the study of ß-sheets: a. Linus Pooling and Robert Corey studied ß-sheets through investigation of α-keratin's structure b. Linus Pooling and Robert Corey studied ß-sheets through investigation of ß-keratin's structure c. Linus Pauling and Robert Corey studied ß-sheets through investigation of α-keratin's structure D. Linus Pauling and Robert Corey studied ß-sheets through investigation of ß-keratin's structure

D. Linus Pauling and Robert Corey studied ß-sheets through investigation of ß-keratin's structure

[Some natural proteins are rich in disulfide bonds, and their mechanical properties (tensile strength, viscosity, hardness, etc.) are correlated with the degree of disulfide bonding.] Glutenin, a wheat protein rich in disulfide bonds, is responsible for the cohesive and elastic character of dough made from wheat flour. Similarly, the hard, tough nature of tortoise shell is due to the extensive disulfide bonding in its α-keratin. What is the molecular basis for the correlation between disulfide bond content and mechanical properties of the protein?

Disulfide bonds are covalent bonds, which are much stronger than the noncovalent interactions that stabilize most proteins. They cross-link protein chains, increasing their stiffness, mechanical strength, and hardness.

steps in a an enzyme substrate reaction

E+S <--> Ezyme Substrate Complex <--> Ezyme Product Complex <--> E+P (enzyme plus product)

What is a helpful mnemonic to remember what the 4 digits of the classification system stand for?

EGAM 1. Enzyme class 2. Group being transferred 3. functional group Accepting transferred group 4. Molecule/compound that accepts the group

Who proposed the lock and key hypothesis?

Emil Fischer

Why are activation barriers crucial for life?

Energy barriers prevent complex macromolecules from simply reverting spontaneously back to their simpler molecular forms. Remember, the rate at which a molecule undergoes a particular reaction decreases as the activation barrier increases. Enzymes have evolved to specifically target the reactions needed at a particular point and time for survival. Found on pg. 192 of textbook.

What happens when non-covalent interactions form between substrate and enzyme?

Energy is released (Binding Energy) that helps lower the activation energy needed

Which His residues are common to all globins?

F8-proximal His E7-distal His

coenzyme examples

FAD NAD yes, like from the Kreb cycle

Which of the following statements are false (circle all that apply)? a. the N-Cα bond angle is called the phi (Φ) angle and the Cα-C bond angle is called the psi (Ψ) angle b. the N-Cα bond angle is called the psi (Ψ) angle and the Cα-C bond angle is called the phi (Φ) angle c. conformations of a polypeptide chain are limited by the partial double peptide bond only d. R groups and the partial double peptide bond play a role in limiting polypeptide chain conformations

FALSE statements: b. the N-Cα bond angle is called the psi (Ψ) angle and the Cα-C bond angle is called the phi (Φ) angle c. conformations of a polypeptide chain are limited by the partial double peptide bond only

[True/False] enzymes cannot be modified

False

true/false, spontaneous folding never involves chaperones

False, in proteins that require chaperons, note that spontaneous folding and chaperone assistance is happening at the same time.

true/false, a chaperonin can fold two proteins at the same time.

False, one chamber is the empty trans chamber while the other is the cis chamber where protein folding occurs. Each chamber may only function for protein folding in a one at a time fashion.

Four digit classification system

First digit: refers to the 1-6 to denote which class the enzymes belong to Second digit: denotes the group being transferred Third Digit: denotes the functional group that accepts the transferred group Fourth Digit: denotes the compound which accepts the transferred group

(adapted from Chapter 4, problem 1) X-ray studies of crystalline peptides by Linus and Pauling and Robert Corey lead to the following key observations: 1) the C-N bonds in peptides is between that of double and single bond 2) all four atoms attached to the C-N group are in the same plane ( they are planar) 3) the alpha carbons are always trans to each other (on opposite sides of the peptide bond). Given these key observations of Dr. Pauling and Dr. Corey, what do you think this means in terms of the strength of the C-N bond and its bond order? Do you think rotation is easy about the C-N bond?

Given the in-between length of the C-N bond in polypeptides Dr. Pauling and Dr. Corey concluded that C-N bonds have partial double bond character. This means their strength is between that of single and double bonds. I also means that rotation is limited or does not occur at all along the C-N bond.

Keq for an exergonic reaction?

Greater than 1

What are the symptoms of altitude sickness?

Headache, fatigue, nausea

What is the cause of sickle cell anemia?

Hemoglobin S instead of hemoglobin A; substitution of valine for glutamate at position 6 on Beta chain (uncharged put where charged should be) This creates insoluble fibers when the hemoglobins stick together Sickled RBCs have shorter lifespan of 10-20 days

Why is the sigmoid curve of hemoglobin advantageous?

Hemoglobin needs to bind with high affinity in lungs and low affinity in tissues so O2 is released to tissues

Why is there such prevalence of sickle cell anemia in Africa?

Heterozygotes for sickle-cell anemia are protected from malaria. The sickle-cell shape interferes with the pathogen life cycle

Where do we see Hsp70 in action? What does Hsp70 do?

Hsp70 typically acts on the intermediates of smaller proteins that fold spontaneously. While these proteins fold, their hydrophobic regions in the intermediate form are not yet protected from water. Thus to prevent agreegation, Hsp70 clamps on and protects the hydrophobic groups.

How do amyloids form in general?

Incompletely folded proteins are produced inside or released from the cell. Before they have a chance to fold correctly, the core region containing many hydrophobic residues form ß-sheets and then interact with other misfolded proteins with hydrophobic ß-sheet cores. Typically regions of ß-sheet formation also contain high concentrations of aromatic amino acid residues that stabilize the ß-core. Slowly the amyloid fibers grow over time as more as more misfolded secreted proteins are excreted into the extracellular matrix.

What initiates the T-R state transition

Initiated by O2 binding, changing the quarternary structure. O2 binding results in His residue at terminal end o the ß-chain rotating inward. Narrowing of pocket between Beta subunits in R state.

how does a prion infect cells?

It bumps and interacts with normal proteins and to change their conformation into the infective and aggregating prion form.

What happens if no matter how much Hsp70 tries and tries again, the protein keeps folding worng?

It hands the protein over to the class of chaperonins.

What is the Keq at equilibrium? What is the delta G here?

Keq =1.0 and delta G =0

Equilibrium Constant

Kₑq = [P]/[S]

Keq for an endergonic reaction?

Less than 1

What mediates an induced fit?

Ligand binding

Who were the two important scientists involved in the discovery of the peptide bonds and protein structure?

Linus Pauling and Robert Corey

What are the partial pressures of oxygen in lungs, tissues, and working muscles?

Lungs: 13kPa Tissues: 4 kPa Working muscles 1.5 kPa

What is the cycle of oxygen in hemoglobin?

Lungs: T state; high PO2 forces O2 pickup, transition to R state Leaves lungs- lower PO2, R state required to keep O2 Tissues: PO2 so low that O2 is released even in R state; loss of O2 causes transition to T state, facilitates O2 release

How does the body combat altitude sickness?

Makes more BPG

Positive cooperativity in hemoglobin permits:

Maximum O2 delivered to tissues

Polanyi Haldane, Pauling, Jenks proposed what to explain for how enzymes interact with substrate?

Modified lock and key model

What effect does low pH have on hemoglobin?

More HC3 (terminal) His is protonated - stabilizes T state - facilitates release of O2

What type of interactions do the alpha and beta chains use to bind?

Mostly hydrophobic Some hydrogen and ionic bonds

What purpose does quaternary structure serve? Why would we want a protein that has different types of subunits? Why would we want proteins with subunits that are all the same?

Multiple different subunits in the same protein are very useful for allowing a single protein to perform many functions at once. (e.g. one subunit of an enzyme is the catalyst while the other is the regulatory subunit) A protein that has many of the same kind of subunit is needed for structural functions. It much easier and more efficient for a cell to produce many of the same component over and over again than to produce a new subunit.

What are allosteric proteins?

Multisubunit, multiple ligand binding sites

Dietary precursor of NAD in mammals?

Nicotinic acid (Niacin)

Does the Keq or delta G determine the reaction rate?

No

Why is hemoglobin not always in the R state?

No O2 released at PO2 4kPa

Do enzymes affect delta G?

No!

What is the normal amount of BPG and what is the amount of someone living at high altitudes?

Normal- 5mM High altitude- 8mM

How to reduce the amount of activation energy needed?

Offset it with Binding Energy

Chymotrypsin

One of the main pancreatic proteases; it is activated (from chymotrypsinogen) by trypsin.

Why is there even an energy barrier in the first place?

Physical and thermodynamic factors listed below make reactions unlikely 1) entropy of molecules -- it is rare that two molecules for a reaction will happen to collide 2) for a reaction to take place, the hydrated barrier/solvation shell around the substrate that keeps its stable will have to be disturbed. 3) the substrate must be distorted and changed to its transition state 4) catalytic groups have to be in perfect alignment in order for an actual reaction and transfer of groups to occur.

What contributes to the need for activation energy?

Physical and thermodynamic factors make reaction "unlikely"

What is the heme prothetic group made of?

Protoporphyrin ring iron-four of the six coordinate bonds are bound to protoporphyrin

ΔG'⁰=-R*T*lnK'eq

R is the gas constant 8.315 J/mol T is the temperature 298K

What is the dietary precursor of FAD in mammals?

Riboflavin (Vitamin B₂)

[In x-ray studies of crystalline peptides, Linus Pauling and Robert Corey found the C-N bond in the peptide link is intermediate in length (1.32 angstrom) between a typical C-N single bond (1.49 angstrom) and a C=N double bond (1.27 angstrom). They also found that the peptide bond is planar (All four atoms attached to the C-N group are located in the same plane) and that the two α-carbon atoms attached to the C-N are always trans to each other (on opposite sides of the peptide bond).] What do the observations of Pauling and Corey tell us about the ease of rotation about the C-N peptide bond?

Rotation about the peptide bond is difficult at physiological temperatures because of its partial double bond character.

Unimolecular Reaction

S<-->P

[In x-ray studies of crystalline peptides, Linus Pauling and Robert Corey found the C-N bond in the peptide link is intermediate in length (1.32 angstrom) between a typical C-N single bond (1.49 angstrom) and a C=N double bond (1.27 angstrom). They also found that the peptide bond is planar (All four atoms attached to the C-N group are located in the same plane) and that the two α-carbon atoms attached to the C-N are always trans to each other (on opposite sides of the peptide bond).] What does the length of the C-N bond in the peptide linkage indicate about its strength and its bond order (ie, whether it is single, double, or triple)?

Shorter bonds have a higher bond order (are multiple rather than single) and are stronger. The peptide C-N bond is stronger than a single bond and is midway between a single and double bond in character.

What are the two major conformations of hemoglobin?

T (tense) less affinity for oxygen, more stable w/o oxygen R (relaxed) high affinity and more stable with oxygen

How does the protoporphyrin ring look in the T vs. the R state?

T state: ring puckered R state: planar

What are the conditions for standard free energy?

Temperature is 298 K, pressure is 101.3 Pa 1 molar solution

Collagen fibrils/supper coils are held by modified lysine called norleucine. What is different about norleucine from lysine?

The amino group at the epsilon position in lysine is gone in norleucine.

Induced fit

The change in conformation of the active site of an enzyme so that it binds more snugly to the substrate, induced by entry of the substrate

the relationship between k and G‡ is inverse and exponential. What is this the basis for?

The lower the activation energy, the higher (faster) the reaction rate, and vice versa

[William Astbury discovered that the x-ray diffraction pattern of wool shows a repeating structural unit spaced about 5.2 angstroms along the length of the wool fiber. When he steamed and stretched the wool, the x-ray pattern showed a new repeating structural unit at a spacing of 7.0 angstroms. Steaming and stretching the wool and then letting it shrink gave an x-ray pattern consistent with the original spacing of 5.2 angstroms. Although these observations provided important clues to the molecular structure of wool, Astbury was unable to interpret them at the time.] Given our current understanding of the structure of wool, interpret Astbury's observations.

The principal structural units in the wool fiber polypeptide (α-keratin) are successful turns of the α helix, at 5.4 angrstom intervals; coiled coils produce the 5.2 angstrom spacing. Steaming and stretching the fiber yields an extended polypeptide chain with the β conformation, with a distance between adjacent R groups of about 7.0 angstroms. As the polypetide reassumes α helical structure, the fiber shortens.

What protein forms amyloids in Huntington's disease? Are these aggregates inside or outside the cell?

The protein huntingtin is involves which is a polyglutamine repeat. It forms aggregates inside the cell.

What happens to the protoporphyrin ring when oxygen binds?

The ring changes shape, pushes on F helix

Which step is the rate limiting step?

The step with the highest activation energy

What configuration does the peptide bond exist in?

The trans configuration (oxygen pointing opposite the amino hydrogen)

There are two main reasons for why the formation of aggregates occurs. what are they? What response is triggered to help alleviate the aggregate formation?

The two reasons include: 1) when synthesis of proteins is too great for the chaperones to keep up 2) when the stress conditions arise that result in too many denatured and misfolded proteins. When aggregates begin clumping, the unfolded protein response (UPR) is triggered.

How do organic solvents such as urea and detergent affect protein structure?

They disrupt the hydrophobic core and lead to denaturation.

What is the advantage of globular proteins having a compact and convoluted pattern?

This folding allows for more diversity necessary for a wide array of functions such as in enzymes, hormones, and defense proteins.

Gly and Pro have an important relationship with the α-helix. Draw the structures of proline and glycine and then explain why each has a bitter relationship with α-helices and is typically not found in them.

This picture here shows proline and glycine drawn in the context of a polypeptide chain. So don't worry if your drawings don't include them in a chain. I just wanted to show a better picture of what they look like in a chain and how this can make and α-helix difficult Explanation: Proline's phi bond between N-Cα is locked in a rigid ring. This does two things: 1) the N atom can't participate in H-bonding, AND 2) the ring is not flexible enough for ring formation. Glycine so small and flexible that it actually is more stable forming its own tighter kind of helix. It makes helices too loose and wobbly.

... was the first to suggest that TSEs were caused by proteins. ...was resonsible for 4 decades of investigation which revealed prion proteins as the culprit of the condition.

Tikavah Alper Stanley Prusiner

First Order reactions (first order rate constants)

V = k[S] V represents the amount of S --> P/unit time

Where does the heme group bind to polypeptides?

Via the His residue on the F alpha helix

What are often the precursors to coenzymes?

Vitamins

[William Astbury discovered that the x-ray diffraction pattern of wool shows a repeating structural unit spaced about 5.2 angstroms along the length of the wool fiber. When he steamed and stretched the wool, the x-ray pattern showed a new repeating structural unit at a spacing of 7.0 angstroms. Steaming and stretching the wool and then letting it shrink gave an x-ray pattern consistent with the original spacing of 5.2 angstroms. Although these observations provided important clues to the molecular structure of wool, Astbury was unable to interpret them at the time.] When wool sweaters or socks are washed in hot water or heated in a dryer, they shrink. Silk, in the other hand, does not shrink under the same conditions. Explain.

Wool shrinks in the presence of moist heat, as polypeptide chains are converted from an extended β conformation to the native α helical conformation. The structure of silk - β sheets, with their small, closely packed amino acid side chains- is more stable than that of wool.

Why is hemoglobin not always in the T state?

Would not pick up enough O2 in lungs, less O2 would be transferred overall

do es and ep have their own activation energy?

YES, but rate limiting step is the step that has the highest activation energy and that one is what is usually being referred to.

can beta sheets stack?

Yes

what helps drive the association of two polypeptide chain to form coiled coil?

a "desire" to avoid interaction with water

Which of these statements are true (circle all that apply)? a. ß-sheets are capable of stacking on top of one another b. 90° ß-turns occur in ß-pleated sheets c. ß-turns are composed of 8aa d. H bonds between C=O and H-N at positions 1 and 4 respectively e. type II ß-turns are more common and we need to know it for the exam as opposed to the less important type I.

a and b are true ß-turns are 180°, ß-turns contain 4aa, and type I is more common and important for us to know.

Which lists contain amino acids that are all commonly found in ß-sheets (circle all that apply)? a. Tyr, Trp, Ile b. Thr, Phe, Arg c. Val, Phe, Pro d. Phe, Val, Thr

a and d are correct

how many H bonds can form in alpha helix (relative answer)?

a lot

multi-subunit proteins range from ... to ... of polypeptides. Each polypeptide equals one ... A few subunits together form ... while many subunits together form ... a. 2, hundreds, subunit, oligomer, multimer b. 200, thousands, subunit, oligomer, multimer c. 2, hundreds, subunit, multimer, oligomer d. 200, thousands, subunit, multimer, oligomer.

a. 2, hundreds, subunit, oligomer, multimer

... is the class of chaperones that play a ... role in protein folding (meaning that these chaperons are involved in preventing wrong folding from happening in the first place). ... is the class of chaperones that play a ... role in protein folding (meaning that these chaperons are involved in promoting proper folding in proteins that don't fold completely on their own spontaneously) a. Hsp70, passive, chaperonin, direct b. Hsp70, direct, chaperonin, passive c. chaperonin, passive, Hsp70, direct. d. chaperonin, direct, Hsp 70, passive

a. Hsp70, passive, chaperonin, direct

In ... ß-sheets, each row has the opposite amino-to-carboxyl orientation. This type of ß-sheet has ... H-bonds that hold the sheets together. In ... ß-sheets, each row has the same amino-to-carboxyl orientation. This type of ß-sheet has ... H-bonds that hold the sheets together? a. antiparallel; vertical; parallel; diagonal b. parallel; vertical; antiparallel; diagonal c. parallel; diagonal; antiparallel; vertical d. antiparallel; diagonal; parallel; vertical

a. antiparallel; vertical; parallel; diagonal

For every false statement, explain why it is false: a. collagen has substantial nutritional value b. collagen is used to make gelatin c. As we age, collagen fibers become more flexible and weaken. d. genetic defects in collagen fibers are caused by random insertions of serine and cysteine residues into the protein. e. each genetic disorder related to collagen is the result of a single substitution that replaces a different glycine located somewhere in the protein.

a. collagen has the same repeating tripeptide unit over and over again. It is not diverse enough to be a nutritonal source. c. As we age, collagen fibers become more rigid and brittle because they accumulate covalent cross-links in collagen fibrils d. All genetic defects related to collagen are the result of a single substitution of a glycine with another amino acid with a larger R group. The tight left-handed helix can't be formed properly and the Gly-X-Y tirpeptide repeat.

Circle all that correctly describe the conformation of an α-helix: a. contains 3.6aa/helical turn and is each helical turn is 0.54nm long b. contains 3.4aa/helical turn and each helical turn is 0.52nm long c. polypeptide planes are perpendicular to the vertical axis of the α-helix d. polypeptide planes are parallel to the vertical axis of the α-helix e. α-helices are typically left handed f. α-helices are typically right handed. g. R groups point outward from the helix h. R groups point inward the helix

a. contains 3.6aa/helical turn and is each helical turn is 0.54nm long d. polypeptide planes are parallel to the vertical axis of the α-helix f. α-helices are typically right handed. g. R groups point outward from the helix

Which of the following statements are true? a. fibrous protein structures were studied first by scientists because they were the simpler and they only contain a single type of secondary structure. b. fibrous protein structures were studied first because they were the simpler and they contain one or more types of secondary structure. c. globular proteins contain only one type of secondary structure. d. globular proteins have structural roles e. α-keratin is soluble in water

a. fibrous protein structures were studied first by scientists because they were the simpler and they only contain a single type of secondary structure.

Myoglobin is an example of a ... protein. It is a relatively small protein with a MW of... and contains... amino acids... More than 70% of myoglobin is made up of exacetly eight ... The rest is made up of sharp bends in the protein in which ... prolines are located at the sharp bends. As is typical, the ... residues are buried in the structure, but what makes myoglobin unique from majority of proteins is a ... group located in the upper middle of the protein. a. globular, 16,700, 153, α-helices, 4, hydrophobic, heme b. fibrous, 16,700, 153, α-helices, 4, hydrophobic, heme c. globular, 18,600, 230, α-helices, 4, hydrophobic, heme d. fibrous, 18,600,230, ß-sheets, 4, hydrophobic, heme.

a. globular, 16,700, 153, α-helices, 4, hydrophobic, heme

Find the false statements and explain why are they false? a. over evolutionary time both the motif and the amino acid sequence of the motif are preserved. b. if I know the domain, I also must know the arrangement of amino acids c. one domain may have multiple motifs d. two domains may have similar or different folding motifs.

a. is false because sometimes is the changes to the amino acid sequence don't affect the motif folding pattern over time. Motifs are thus an additional way to study evolutionary relationships outside of genome sequences. b. is false. The motifs within the domain reveal the arrangement of the amino acids inside a domain.

... is an example of an intrinsically disordered protein which is responsible for locating ... in DNA. What feature of this protein allows it to respond in different ways to what it finds in the DNA? a. p53, damage, its C termini binds to at least 4 different ligands that either help signal for DNA repair or apoptosis b. p53, duplications, its C termini binds to at least 4 different ligands that either help signal for DNA repair or apoptosis c. p27, damage, its C termini binds to at least 4 different ligands that either help signal for DNA repair or apoptosis d. p53, damage, N termini binds to at least 4 different ligands that either help signal for DNA repair or apoptosis

a. p53, damage, its C termini binds to at least 4 different ligands that either help signal for DNA repair or apoptosis

Concerning secondary structures, what statement is FALSE? a. recurring arrangements in space of amino acids anywhere in the polypeptide chain b. secondary structure relies on non-covalent interactions c. secondary structures relies on types of amino acids d. recurring arrangements in space of adjacent/local amino acids e. a and c are false

a. recurring arrangements in space of amino acids anywhere in the polypeptide chain

α-keratin has a ...-handed and ... α-helix with ... amino acids per turn. Collagen has a ...-handed and ... α-helix with ... aa per turn. a. right, looser, 3.6, left, tighter, 3 b. right, tighter,3, left, looser, 3.6 c. left, looser, 3.6, right, tighter, 3 d. left, tighter, 3, right, looser, 3.6

a. right, looser, 3.6, left, tighter,3

find the false statements and correct them. a. fibrous proteins are only good for strength. b. silk fibroin has antiparallel ß-sheets that contain large R groups such as trp and phe. c. silk fibroin contains antiparallel ß-sheets that pack tightly together to provide strength to the protein. d. silk fibroin is both flexible and very stretchy

a. this is false because they are good for both flexibility and strength b. is false because Gly and Ala are actually the most common amino acids present in sild fibroin which are small and allow for tight stacking of ß-sheets. d. is false. While it is true that the antiparallel ß-sheets are very flexible in fibroin due to hydrogen bonding, it is not true that fibroin is strechy. ß-sheets are already in as stretched out conformation as the protein can be in. Flexible in this case means that the ß-sheets are capable of breaking and reforming. But stretching is something that can only be done with α-helicies that are not in their fully extended state.

which types of amino acids help to stabilize alpha helix?

aa with oppositely charged R GPS 3-4 as away aa with hydrophobic r groups 3-4 as away

about how long does it take chaperonin to fold a protein properly?

about 10s

How can the rate of reaction be increased?

add heat use a catalyst to lower the activation energy needed

where is alpha keratin found in mammals?

almost all of dry weight of scales, hooves, hair, feathers, outer layer of skin

Huntington's disease, Parkinson's, type 2 diabetes, and Alzheimers are all called .... because they involve the formation of insoluble extracellular fibers called....

amyloidoses amyloids

Catalytic functional groups provide what?

an alternative, lower energy reaction pathway for formation of products

Prosthetic Group

an organic compound/metal ion that is very tightly bound or covalently bound

Peptide group

atoms lying in the same plane

About .. of all human proteins lack structure. In contrast to ordered proteins, they lack ... and posses... While much still needs to be known about these intrinsically disordered proteins, it is believed that the purpose of their odd and disordered structure is to provide... a. 1/4, hydrophobic core, many charged amino acids and proline residues, flexibility to interact with more than one substance b. 1/3, hydrophobic cores, many charged amino acids and proline residues, flexibility to interact with more than one substances. c. 1/4, hydrophobic cores, many charged amino acids and proline residues, rigidity to provide structure. d. 1/3, hydrophilic cores, many nonpolar residues, flexibility to interact with more than one substances.

b. 1/3, hydrophobic cores, many charged amino acids and proline residues, flexibility to interact with more than one substances.

Which of theses statements is false about he super helix in collagen? a. It is formed by the coiling of 3 left-handed α-helices together to form a mega right-handed super helix. b. It is formed by the coiling of 3 left-handed α-helices together to form a mega left-handed super helix. c. other names for the super helix include fibril or tropocollagen d. the super helix gives collagen enormous tensile strength up to 10,000x its own weight.

b. It is formed by the coiling of 3 left-handed α-helices together to form a mega left-handed super helix.

Which of these statements is/are false and why? a. domains are able to fold independently from each other into thermodynamically stable structures. b. It is not possible that a motif can be made of only one type of secondary structure (For example two or more α-helicies does not count as a motif) c. common motifs include the ß-α-ß loop and the ß-barrel d. The PDB is the Protein Domain Bank which has more than 100,000 protein structures that are sorted into 4 categories based off their protein structure.

b. Motifs just have to contain more than one secondary structure, not two different types of secondary structure. It doesn't matter whether you have all α or ß, just as long as you have two or more ß-sheets or α-helices, you could have a motif. d. PDB stands for Protein Data Bank not Protein Domain Bank

Which of the following are amino acids that we typically see in bends? a. Pro, Gly, Ser, Tyr b. Pro, Gly, Ser, Thr c. Pro, Gly, His, Thr d. Pro, Gln, Ser, Thr

b. Pro, Gly, Ser, Thr

... is the compact region that is a distinct structural unit within a larger polypeptide chain. On the other hand, ... is a recognizable folding pattern involving 2 or more elements of secondary structure and the connections between them. a. motif, domain b. domain, motif c. tertiary structure, secondary structure d. secondary structure, tertiary structure.

b. domain, motif

In type I ß-turns, glycine is commonly found because it is very... Meanwhile, proline is often found because it is capable of two isomers due to the ... nature of the peptide bond. This often leads to the N atom having a ... which then causes proline's ring to break and flip into a different stereoisomer. The ... isomer is typically found in ß-turns while normally the ... isomer is the preferred form seen in protein chains. a. rigid; partial double bond; positive charge; cis; trans b. flexible; partial double bond; partial positive charge; cis; trans c. rigid; partial double bond; partial positive charge; trans; cis d. flexible; partial double bond; positive charge; cis; trans

b. flexible; partial double bond; partial positive charge; cis; trans

Which of the following statements are true (circle all that apply)? a. primary and secondary structure is heavily reliant on covalent bonds while tertiary structure if reliant on noncovalent bonding b. primary structure is reliant on covalent bonding while tertiary and secondary structures are reliant on noncovalent bonding. c. dehydration synthesis forms secondary structures. d. dehydration synthesis is required for the primary structure to form.

b. primary structure is reliant on covalent bonding while tertiary and secondary structures are reliant on noncovalent bonding. d. dehydration synthesis is required for the primary structure to form.

When hair is permed, the hair is first wrapped and bent into its desired shape. The hair must then be treated with a reducing agent that contains ... or .... This first step is important for ... the cross-links between α-keratin proteins formed by ... Heat is then used to break all the ... bonds of the α-helices. At the end of this process an oxidizing agent is added and the hair is cooled to allow reformation of the bond broken. Hair fibers will now be curled because new ... bonds are formed where they were not before. a. thiol, sulfhydryl groups (-SH), forming, disulfide bonds, hydrogen, disulfide b. thiol, sulfhydryl groups (-SH), breaking, disulfide bonds, hydrogen, disulfide c. thiol, sulfhydryl groups (-SH), breaking, hydrogen bonds, disulfide, disulfide d. thiol, sulfhydryl groups (-SH), breaking, hydrogen bonds, disulfide, hydrogen bonds.

b. thiol, sulfhydryl groups (-SH), breaking, disulfide bonds, hydrogen, disulfide

why doesn't fibroin stretch?

beta conformation is already in extended form

why is fibroin flexible?

beta sheets are held together by hydrogen bonds NOT covalent bonds covalent bonds provide strength

Where did prion name come from?

both options are correct with Dr. Barone: 1) proteinacious infectious = prion because Dr. Prusiner thought it sounded better to switch the o and i. 2) proteinacious infectious only protein = prion

What is the technical name for mad cow disease?

bovine spongiform encephalopathy (BSE)

what limits the number of combos

bulkiness of r group lack of freedom of rotation around the peptide bonds (no rotation around double bond

Which of the following are TRUE: a. Linus Pauling and Robert Clives studied α-helix structure through α-keratin b. Linus Pauling and Robert Clives studied ß-helix structure through α-keratin c. Linus Pauling and Robert Corey studied α-helix structure though α-keratin d. Linus Pauling and Robert Corey studied α-helix structure through ß-keratin

c. Linus Pauling and Robert Corey studied α-helix structure though α-keratin

The structure of a globular protein can be described as: a. compact b. convoluted pattern c. compact and convoluted pattern d. loose and expanded

c. compact and convoluted pattern

Quaternary structures are held together by a. covalent bonds b. disulfide bonds c. noncovalent bonds d. non of these

c. noncovalent bonds

What is the correct order of the structures α-keratin can form? a. α-helix of α-keratin → two-chain coiled coils → protofibrils → protofilaments → intermediate filaments b. α-helix of α-keratin → two-chain coiled coils → protofibrils → intermediate filaments → protofilaments c. α-helix of α-keratin → two-chain coiled coils → protofilaments → protofibrils → intermediate filaments d. two-chain coiled coils → α-helix of α-keratin → protofilaments → protofibrils → intermediate filaments

c. α-helix of α-keratin → two-chain coiled coils → protofilaments → protofibrils → intermediate filaments

glycoprotein prosthetic group

carbohydrates

carbon based (organic) cofactor

coenzyme

Some enzymes require the presence of [blank] to function

cofactors

This type of protein is found in connective tissue such as in tendons, cartilage, matrices of bones, and the cornea of the eye.

collagen

Holoenzyme

complete, catalytically active enzyme together with its cofactor

What are coenzymes?

complex organic or metalloorganic molecules that assist enzymes in their function.

[S]

concentration of substrate

which amino acids are involved in forming noncovalent bond? (hydrophobic, h bonds, Ionic interactions)

core atoms (NH and CO) as well as R group atoms

what type of bond forms between tropocollagen

covalent bond dehydrohydroxylysinonorleucine bonds this is between 2 modified lysines

The iron atom in the heme group is able to form ... coordinate bonds. ... is/are bound to the protoporphyrin ring, ... is/are open to bind to O2, and ... is/are bound to the ... amino acid of the protein portion of myoglobin or hemoglobin. a. 6, 4, 1, 1, Ser b. 6, 1, 1, 4, His c. 4, 2, 1,1 Ser d. 6, 4, 1, 1, His

d. 6, 4, 1, 1, His

which are NOT true descriptions of chaperones a. proteins that interact with partially or improperly folded proteins to facilitate correct folding b. provide a microenvironment to facilitate correct folding c. can help some protein aggregates to their folded sate d. Hsp60 and chaperonins are the two classes of chaperones

d. Hsp60 and chaperonins are the two classes of chaperones Hsp70 and chaperonins are the two classes of chaperones.

What bonds play a major role in the native form of a protein? a. hydrophobic interactions b. hydrogen bonds c. ionic interactions d. both a and b e. both b and c

d. both a and b

All of the following EXCEPT... hold native structures together: a. hydrogen bonds b. hydrophobic forces c. ionic bonds d. covalent bonds (with the exception of disulfide bonds) e. van der Waal interactions f. both d and e

d. covalent bonds (with the exception of disulfide bonds)

Which of the following is not something that will lead to protein denaturation? a. heat b. organic solvents. c. extreme pH d. freezing

d. freezing

α-keratin and collagen have some bizarre qualities including its... in water. This is because it has ... residues on the outside as well as in the inside of the protein. To counteract the instability created by its unusual structure, α-keratin and collagen do something else peculiar. It uses ... bonds to form chains, called ... Other proteins preferably rely on ... bonds for their tertiary structure. a. solubility, hydrophobic, covalent bonds, covalent, supramolecular complexes, noncovalent bonds. b. insolubility, hydrophobic, noncovalent bonds, covalent, supramolecular complexes, covalent bonds c. insolubility, hydrophilic, covalent bonds, covalent, supramolecular complexes. d. insolubility, hydrophobic, covalent bonds, covalent, supramolecular complexes, noncovlaent bonds

d. insolubility, hydrophobic, covalent bonds, covalent, supramolecular complexes, noncovalent bonds

Which of the following facts about vitamin C and scurvy are false? a. another name for vitamin C is L-ascorbic acid (ascorbate) b. Scurvy wouldn't be a problem if humans hadn't lost the genes to synthesize vitamin C over evolutionary time. c. vitamin C is sourced from peppers, tomatoes, potatoes, and broccoli d. scurvy is the result of vitamin C overload which disrupts of functioning of hydroxylation of proline and lysine in collagen. e. without vitamin C, lysine and proline are not hydroxylated

d. is false because actually it is vitamin C deficiency which prevents the hydroxylation of proline and lysine.

Choose the most complete definition of the primary structure? a. it is the sequence of amino acids that make up a polypeptide/protein b. it is the type and order of amino acids in a sequence of a polypeptide chain/protein c. it is a chain of amino acids and the location of where disulfide bonds will form d. it is the type and order of amino acids in a sequence of a polypeptide chain/protein, and the location of where disulfide bonds will form.

d. it is the type and order of amino acids in a sequence of a polypeptide chain/protein, and the location of where disulfide bonds will form.

Which is NOT a common amino acid that occurs in ß-sheets? a. Phe b. Val c. Thr d. Ser

d. ser

chronic wasting disase is a transmissible spongiform encephalopathies (TSEs) that occurs in...

deer and elk

How are amino acid monomeic subunits are linked together by?

dehydration synthesis and peptide bonds

norleucine

derived from lysine (4 cH2 with NH3) norleucine is 4CH groups

What is the special type of bond that holds collagen fibrils together in a staggered fashion? What two amino acids are involved in this bond?

deydrohydroxy lysino norleucine bond This cross-link bond is formed between two modified lysine amino acids. One is converted to norleucine (its amino group is striped from it). The other is a hydroxylated leucine and is shown in pink in the picture on this card.

in order to hold protofibrils/protofilaments/coiled coils together what is used?

disulfide bonds up to 18% of total residues are cysteine

Select the true descriptions/characteristics of a peptide bond? a. it is a partial double bond and it is intermediate in length between single and double bonds b. it is planar and no rotation can occur about it c. N is trans to O e. a, b, and c are true f. only a and c are true

e. a, b, and c are true

Both α-helices and ß-helices contain many hydrogen bonds holding them together. What atoms are most responsible for these hydrogen bonds? a. The O-H group in serine and the N-H group in asparagine b. the hydroxyl group in threonine and the amido group in asparagine c. the O-H group in serine and the N-H group in glutamine d. the O-H group in threonine and the N-H group in glutamine e. the C-O group in the peptide bond and the N-H group in the peptide bond.

e. the C-O group in the peptide bond and the N-H group in the peptide bond.

antiparallel beta sheet

each row has an opposite amine to carbonyl conformation

parallel beta sheet

each row has the same amine to carbonyl orientation

is it easy or difficult to unfold noncovalent forces?

easy because they are weak

activation energy

energy needed to overcome energy barrier and reach transition state

example of a globular protein

enzyme

reaction intermediates

es (enzyme substrate complex) and ep (enzyme product complex)

True/false. cystic fibrosis is considered an amyloidosis disease

false

true/false, all protein misfolding leads to amyloid formation

false

true/false, only eukaryotes have chaperonins as a class of chaperones to help with protein folding.

false, 15% of e. coli proteins require chaperonins

tropocollagen

fibrous protein consisting of three left handed helices twisted together and containing large amounts of glycine, proline, and hydroxyproline provides enormous tensile strength

which protein was studied first? globular or fibrous

fibrous, all parts of protein are similar to each other so they are simple

What is FAD?

flavin adenine dinucleotide, a coenzyme

each amino acid in beta sheet can do what?

form hydrogen bonds between rows for both parallel and antiparallel

Ligases 6

formation of C-C, C-S, C-O, and C-N bonds by condensation reactions coupled to cleavage of ATP or similar cofactor ​

How many polypeptide chains/subunits make up hemoglobin? Hemoglobin is an example of which level of protein organization and structure (1°,2°, 3°, or 4°)?

four, quaternary protein structure

enzymes enhance rate of reaction how much?

from hundreds or thousands of years to milliseconds

where did transmissible spongiform encephalopathies (TSEs) get their name?

from the holes that arise in brain tissue from the disease where neurons died

What is the structure of hemoglobin?

globin group and heme group

for propensity of aa to occur in a secondary structure, what do the numbers mean?

greater than 1, common less than 1, less common very small, (ex 0.5) means not very common

lipoprotiens

has lipid prosthetic group

What special chemical is produced by sickle-shaped RBCs?

hemoxygenase

relationship between activation energy and rate of reaction?

higher activation energy, slower rate of reaction and vice versa

kuru and variable Creutzfeldt-Jakob disease (vCJD) are transmissible spongiform encephalopathies (TSEs) that occur in... Why is it important that we specify variable for vCJD?

humans There is a form of Creutzfeldt-Jakob disease that is heritable but the variable form is caused by prions and it is important to use the word variable to specify this fact.

What causes secondary structures?

hydrogen bonds forming between atoms of the polypeptide backbone

what happens when supertwist forms?

hydrophobic as residues interact to cause tight packing trying to avoid contact with water

hydroxylysine

hydroxylated lysine

As ΔG⁰ (KJ/mol)ᵃ [increases/decreases] the amino acid residue will have greater difficulty taking up the α helical conformation

increases

cofactor can be either of 2 things

ion (copper, zinc, magnesium, etc) complex organic or metalloorganic molecule (carbon based)

Where did Hsp70 get its name?

it is one of many heat shock proteins that are highly expressed to protect the hydrophobic residues exposed due to denaturing of proteins under heat or other stressors.

Mathematical link between activation energy and rate

k = kT/h (e-ᵍ‡/ʳᵗ) k is the Boltzman constant h is Planck's constant

partial double bond evidence

length (single=0.154, double=0.134nm, partial is between these) partial charges

Substrate

ligand that binds to an enzyme

Peptide bond

link between carboxyl group and amino group

who elucidated our understanding of the peptide bond?

linus and pauling

problem with adding heat to speed up reaction

living organisms are isothermic and so we can't just heat ourselves up to do this (except fever) and too hot is dangerous for humans

what causes parallel conformation in beta sheets?

loops all the way around from carbonyl on the right to amine group on left

Why does low pH facilitate the release of oxygen?

lower pO2 lower pH, His is protonated, ionic bond with aspartate stabilizes T state another source of H+ in tissue

Proteostasis

maintenance of steady-state collection of active proteins in a cell that involves synthesis, folding, refolding (if necessary), and degradation

enzyme function

making or breaking bonds of a substrate to produce a product lower activation energy to speed up reaction

metal catalysis

metal catalysis = an enzyme bound to a metal an enzyme bound metal can form ionic interactions with a substrate, which helps to orient a substrate for reaction and stabilize charged intermediates an enzyme bound metal can also accept/donate electrons

How does the ubiquitin proteasome system work to degrade misfolded or denatured proteins?

misfolded/denatured protein is labeled with ubiquitin. The proteasomes are designed to recognize the tagged ubiquitin on the proteins. The proteasomes then degrade the ubiquinated proteins into fragments.

This protein stores O2 in muscle, provides O2 to O2 starved tissues, and functions in whales, porpoises, and seals so that they may stay emerged under the water for long periods of time.

myoglobin

most thermodynamically stable form of a protein

native form

What is NAD?

nicotinamide adenine dinucleotide, a coenzyme

How does the enzyme - via noncovalent interactions- reduce the activation energy needed?

noncovalent bond formation results in the release of energy that counteracts the activation energy needed to reach the transition state. This is the main source of energy used by enzymes to lower the activation energy.

where do h bonds form in alpha helix

o of a peptide bond of one as with the HN of a peptide bond of another as that is 3-4 as away every coil has several H bonds holding it in place

... is an example of an intrinsically disordered protein which is responsible for binding to and inhibiting many of the kinases and other signaling molecules involved in signaling cell division. Poorer cancer prognosis is predicted for patients who have ... levels of this protein. a. p27, high b. p53, high c. p53, low d. p27, low

p27, low

All the atoms lying in the same plane along with the atoms involved with the peptide bond are called the ...

peptide group

biochemical standard free energy

performing reaction at pH 7 (physiological condition) 298K 101.3kpa gas pressure 1 molar

Denaturation of albumin is [permanent/reversible]?

permanent

Denaturation of protein due to heat and pH changes often cause what in aqueous solvents?

precipitation

which two aa are rarely found in alpha helix?

proline and glycine

Renaturation

proteins spontaneously refold into the correct structure, with function COMPLETELY restored

... refers to the the spatial arrangement of protein subunits

quaternary structure

partial charge on partial double bond is caused by?

resonance because the double bond flips back and forth between the CO and the CN, setting up an electric dipole

Denaturation of ribonuclease A is [permanent/reversible]?

reversible

The disordered structure of intrinsically disordered proteins provides for the flexibility in binding to other atoms and molecules. For this reason, some intrinsically disordered proteins function as ... or AKA... proteins that scoops up small molecules and ions when they are not needed.

scavengers or AKA "garbage dump" proteins

Rate constant (k) units

sec-¹

scrapie is a transmissible spongiform encephalopathies (TSEs) that occurs in...

sheep

What is the protein that is found in silk and spider webs?

silk fibroin

Because most of the protein molecules in people with an amyloidoses fold normally, the onset of symptoms often occurs...

slowly

What is the CASP?

the Critical Assessment of Structural Prediction. It is a contest to determine the structure of proteins.

Which chains in hemoglobin have lots of contact?

the alpha and beta chains (19aa b/n a1/B2, 30 aa for a1/B1)

Both models of the enzyme-ssubstrate interaction involve what?

the concept of forming non-covalent interactions between E(nzyme) and S(ubstrate)

what is the enzyme plus substrate called

the enzyme substrate complex

What is the active site

the place where substrate binds

Is this a complete statement of what a primary structure is? The primary structure is the type and order of amino acids in a sequence. If so, what is missing?

the primary structure also lays out where disulfide bonds will be formed.

Apoenzyme (AKA apoprotein)

the protein portion of a holoenzyme

Define conformation in terms of proteins

the spatial arrangement of atoms in a protein or any part of a protein

2 classifications of proteins are based on what?

the tertiary structure they are globular or fibrous

primary reason for ingestion of vitamins

they are precursors to coenzyme, so you can't have coenzyme activity without them

What do R groups help with?

they help to stabilize/destabilize/promote the secondary structures

why are pro and gly common in beta turn?

they promote turning

why can phe, tyr, aromatic trp, Ile, Thr, and Val be present in beta sheets even though they are bulky?

this is related to stacking allowing more room for bulky groups to exist, but we aren't sure

What is binding energy used for?

to offset the activation energy required for uncatalyzed reaction

transition state

top of energy barrier (energy barrier prevents reaching transition state) occurs when bonds are bent and things happen in substrate that allow reaction to proceed cannot be isolated

what configuration do peptide bonds in proteins exist in?

trans configuration

transferase 2

transfer functional groups

Oxidireductases 1

transfer of elctrons (hydride ione or H atoms)

hydrolases 3

transfer of functional groups to water and split water via hydrolysis

isomerase 5

transfer of groups within a molecule to yield isometric forms

nicotinamide adenine dinucleotide (NAD)

transient carrier of the hydride ion in the Krebs cycle

True/false, all coenzymes are cofactors, but not all cofactors are coenzymes

true

[True/False] enzymes must maintain native structure to be functional

true

true/false, Hsp70 is a class of chaperones that is only found in eukaryotes

true

beta turn type 1 is more or less frequent than type 2?

twice as frequent as type 2 ​

how is alpha keratin strength amplified?

two alpha helices wound around each other to form a 'coiled coil' that forms a left-handed supertwist

protofilament

two coiled coils associating with each other

protofibrils

two protofilamemts associating

What are enzymes made of?

usually proteins, but a small collection are RNA (ribozymes)

are peptide bonds covalent?

yes

Can partial unfolding be enough to classify a protein as denatured?

yes if it causes loss of function

is there freedom of rotation around the bonds in polypeptide chain?

yes, around psi and phi bonds

This type of fibrous protein is typically found in skin, nails, horns, claws, and hooves?

α-keratin

What protein forms amyloids in Parkinson's disease? What are the aggregates called in Parkinson's. Are these aggregates outside or inside the cell?

α-synuclein creates spherical aggregates called Lewy bodies. Lewy Bodies form inside the cell.

How do enzymes lower activation energy?

•Utilize non-covalent interactions between E and S •Utilize transient covalent bonds and group transfers between E and S

The rate of a rection is determined by what?

•concentration of substrate [S] •rate constant (k) •for a given unimolecular reaction: S<-->P •rate linked mathematically to activation energy (inversely in an exponential relationship)

Models of enzyme-substrate interaction

•lock and key •modified lock and key

Substrates and enzymes have complementary what?

•size •shape •non-covalent binding interactions with the transition state of the substrate