BIO131 #2

hydrophobic interactions

amino acids with nonpolar side chains end up in clusters at the core of the protein, out of contact with water; caused by the action of water molecules, which exclude nonpolar substances as they form hydrogen bonds with each other and with hydrophilic parts of the protein

amino acid residues

an amino acid in a polypeptide that is not the N or C terminal AA

Allosteric Regulation

binding there changes the shape of the enzyme in a way taht makes the active site accessible or inaccessible

nucleotide

building block of a nucleic acid (DNA and RNA)

nitrogenous base

carbon ring structure found in DNA or RNA that contains one or more atoms of nitrogen; includes adenine, guanine, cytosine, thymine and uracil

uracil

one of the four bases that combine with sugar and phosphate to form a nucleotide subunit of RNA; uracil pairs with adenine

Denatured

unfolded by treating it with compounds that break hydrogen bonds and disulfide bonds - can no longer function normally

Primary Structure

unique sequence of amino acids in a protein

side chain interactions

what are the interactions that form the tertiary structure

Molecular Chaperones

-folding is often facilitated by these proteins - part of heat-shock protein family - speed the refolding of other proteins into their normal shape after denaturation has occurred

purine

One of two families of nitrogenous bases found in nucleotides. Adenine (A) and guanine (G) are ______

thymine

The base that pairs Adenine in DNA

Catalysis

*catalyze - speed up chemical reactions -carbonic anhydrase molecules in red blood cells are catalysts *Enzyme - protein that functions as a catalyst

Dehydration Reactions

*monomers polymerize through condensation reactions *newly formed bond results in the loss of a water molecule *hydrolysis is reverse reaction, breaks apart by adding a water molecule

Proteins

*polypeptides that contain 50 or more amino acids consist of single polypeptides or multiple polypeptides that are bonded to one another *catalysis, defense, movement, signaling, structure, transport

beta sheet

, ).is a stretch of amino acids typically 5-10 amino acids long whose peptide backbones are almost fully extended. The association of beta sheets has been implicated in the formation of protein aggregates and fibrils observed in many human diseases, notably the amyloidoses.

alpha helix

- Right-handed helix with 3.6 amino acids/turn - Stabilized by hydrogen bonds between carbonyl O and amide N of residues i and i+4 - H bonds parallel to helix axis Side chains project radially outward to minimize steric repulsion NOTE: Amphipathic α-helix Located at protein surface, hydrophilic R-groups project out into solvent & hydrophobic R-groups project inward to protein core Alpha helix is stabilized by hydrogen bonds. Alpha helix is self assembling. Where else do we find molecules adopt helical DNA or RNA (viruses).

Quaternary Structure

- combination of polypeptide subunits - bonds and other interactions between R-groups, and between peptide backbones of different polypeptides; depends on primary structure

Nature of Side Chains

-aminos have carbon atom bonded to amino group, a hydrogen atom, and a carboxyl group. -properties of amino acids vary cause r-groups vary -Non polar side chains -polar side chains - electrically charged side chains

Structure of Amino Acids

-composed of 20 different building blocks -NH2 - amino functional group - COOH - carboxyl functional group - H - a hydrogen atom - "R-group" - group of atoms called side chain *charges -- help amino acids stay in solution, where they interact with one another and with other solutions and they alter amino acids chemical reactivity

Secondary Structure

-distinctively shaped sections of proteins that are stabilized largely by hydrogen bonding that occurs between the carbonyl oxygen of one amino acid residue and the hydrogen on the amino group of another - alpha helix & beta pleated sheet -- which one depends on molecule's primary structure (geometry & properties of the amino acids in the sequence) -carbonyl group has a partial negative charge due to its high electronegativity & amino has a positive charge bc of its bonded to nitrogen - the amount of hydrogen bonds makes these structures very stable

Tertiary Structure

-polypeptide results from interactions between R-groups or between R-groups and peptide backbone - bc each contact between R-groups causes the peptide bonded backbone to bend & fold contributes to the 3-D shape - 5 types of interactions * Hydrogen bonding - to negative side * Hydrophobic interactions * van der Waals interactions - once hydrophobic side chains are close to one another, they are stabilized by electrical attractions * Covalent Bonding - has disulfide bonds which are bridges *Ionic bonding

Amino Acids & Polymerization

-produced when volcanic gases are put into a glass flask and exposed to the types of high-energy radiation found in sunlight - meteorites (produced in outer space)

HIEARCHY OF PROTEIN STRUCTURE

1) Primary structure Amino acid sequence of a protein, reflects corresponding mRNA sequence Determines both structure and function of a protein 2. Secondary structure Recurring patterns of polypeptide folding Stabilized by hydrogen bonds between backbone carbonyl oxygens and amide nitrogens 3. Domain Smallest thermodynamically stable unit of protein structure Arises from association of secondary structural elements 4. Tertiary structure Comprised of 1 or more domains Final 3D structure of an individual polypeptide (smallest complete unit) 5. Quaternary structure Individual tertiary structures (subunits) assembled into complex polymers

Where enzymes reactants take place

1) collide in a precise orientation 2) have enough kinetic energy to overcome repulsion between electrons that come into contact as a bond forms

Chemical Theory Steps

1- begins with the production of small organic compounds such as H2CO and HCN, from reactants such as H2, CO2, & NH3. 2- Organic compounds reacted to form the mid-sized molecules called amino acids, nitrogenous bases, and sugars. 3- building-block molecules linked to form the types of large molecules found in cells today, including proteins, nucleic acids, and complex carbohydrates. 4- life became possible when one of these large, complex molecule made copy of itself.

amino end

N-terminus

Limits a Rate of Catalysts

1. low concentration = slow linear fashion 2. intermediate concentration level = increase of speed begins slow 3. high concentration level = plateaus at a max speed

alpha helix

A spiral shape constituting one form of the secondary structure of proteins, arising from a specific hydrogen-bonding structure.

IONIZABLE GROUPS

Amino acids are charged Because these groups can act as acids or bases, their protonation state will change depending on environment. Histidine into a soln with HCL. Under these acidic conditions, all groups will be protonated. Now we start adding base. At this first state, histidine is giving up proton (then it flattens, because by adding proton leads to acidity again). So the first group is the carboxyl group. Then we have another, now it is side chian Now alpha amino group will give it up. The red circle around the one with net char = 0. now to find out at which pnt of ph do we have this form. Roughtly 7.5 so pi = 7.5. AT what ph does protein no longer move through electric field.

How enzymes Work

Active site - where the substrates bind and react *enzymes goes under a change of shape with substrate binds to active site (induced fit) *held there by hydrogen bonding or other electrical interactions with amino acids in active site -Once bound, one or more R-groups come into play *interactions with R-group stabilizes the transition state and lowers the activation energy required for the reaction to proceed

sulfur containing amino acid side chains

Amino acids with sulfers (methionine) sulfer can undergo oxidation (spont from environment or like tobacco smoke). Body doesn't want this but it can happen. To it be oxidized, it makes bonding less strong. Can happen impaired protein function in antitrypsin. IMPAIRED PROTEIN FUNCTION Cysteine, thiol group subjected to intended oxidization. Disulfide bonds are imp for blood or intenstine to keep bonds stable in harsh settings. STABILITY

amino acids classifications

BASED ON R GROUP hydrophobic 1) aliphatic: side chain comprised of saturated, linear hydrocarbon backbone: glycine, alanine, valine, leucine, methionine, isoleucine, proline (has ring, structurally makes polypeptide rigid) 2) aromatic - side chain has unsaturated aromatic ring (absorb UV light - important for biochemistry exp) phenaline, tyrosine, tryptophan HYDROPHILIC 1) uncharged: aliphatic side chain contains uncharged polar group serine, cysteine, threonine, glutamine aspergine 2) charged, polar group lysine, histadine (can be neutral or charged) , argenine, glutamate and aspartate

carboxyl end

C-terminus

Catalysts

Enzymes that lowers the activation energy of a reaction and increases the rate of the reaction *is not consumed in the reaction -- composition is the same after as it was before

FIBROUS vs GLOBULAR

Imp = different functions Fib: elongated, rod shaped, provide support, shape and protection, enriched in specific AA, one type of secondary structure dominates. EXAMPLE: collagen, extracellular matrix protein that provide tensile strenght, most abundant protein, compromised of repeating sequence of GLYXY (x is often proline and Y is often hydroxyproline or hydroxylysine - need vitamin C) 3 SUBUNITS WRAPPED AROUND, TRIPLE HELIX. - glycine fits into tight spaces in triple helix core and proline causes kinks and hydroxyproline and hydroxylysine stablize triple helix VIA h bonds. GLOBULAR: spherical, enzymes, very heterogenous AA, mixture of secondary structures. EXAMPLE: trypsin, digestive enzyme in small intenstine excreted by pancrease. cleaves proteins. alpha and beta, loops.

domains and tertiary and quartenary

NOTE: Domain/tertiary structure overlap. Small polypeptides consist of a single domain (domain = tertiary structure). Larger polypeptides tend to be comprised of multiple domains that fold independently. Domain is a unit of protein that folds by itself. All we care about is when u look at this structure you see there are two types of proteins. One loop on top and one at bottem. If you cleave the middle, they would retain their structure. Phosphokinase 1 has two domains. Because are self relying. often domains are particular regio domains carry out specific function, phosphokinase binds sugars and another atp. Allows domans to come together to make new properties. Small proteins carry only one domain Tertierry structure and domain is the same. Multiple polypeptide chains (a.k.a. subunits) assemble into a supra-molecular complex Number of subunits informs name, i.e. dimer (2), trimer (3), etc. May consist of identical (homooligomeric) or different (heterooligomeric) subunits NOTE: Proteins consisting of a single polypeptide chain have no quaternary structure and are referred to as monomers.

Protein Structure

Primary Secondary Tertiary Quaternary

5. Molecular and Functional Bases of Protein Isoforms

Protein isoforms: Alternate forms of a protein Allows organism to create multiple variants of a protein based on a single template Mechanism of Production 1) Multiple genes Functionally-related gene family Duplication and variation of 'ancestral' gene Example: Globin gene family hemoglobin Globin genes that give rise to hemoglobin. That carries oxygen. All these globin gene started with the same gene, but then through mutations we got specific them. Different varients of them by picking them. Isoforms. Controlled by gene expression. Only certain genes will be selected 2. Alternative splicing Different forms of protein encoded by same gene Exons spliced together in different ways EXAMPLE: GLUT TRANSPORTERS Family of 14 transmembrane proteins Function: Transport sugars (e.g. glucose) across plasma membrane by facilitated diffusion (i.e., along concentration gradient) Different isoforms are expressed in different tissues Isoforms differ in their catalytic properties and their regulation Glucose is imp metabolite. There are different proteins that form different glut transporters. Protein family. Glut 1 need lots of it (HIGH AFFINITY, RBCs and brain) Glut 2 doesn't have ahuge affinity but can move it quickly (live, pancrease) Glut 3 is same as glut 1 (neurons) Glut 4 is stimulated by insulin. (adipose tissue, muscle)

groEL

Protein shows you levels of structure. Appreciate the large protein above - 14 identical subunits. That's one domain on the right Quaternary structure: 2 rings comprised of 7 subunits each Each subunit (tertiary structure) consists of three separate domains Each domain, if physically separated, would retain its thermodynamic stability and structure APPRECIATE

beta sheet

Strands of polypeptide in parallel/antiparallel alignment Stabilized by H bonds (co-planar with sheet) H bonds between carbonyl O and amide N from different regions of polypeptide Side chains alternately project above & below plane of sheet Depending on strand orientation, sheets can be parallel, anti-parallel, or mixed Not a flat sheet, but warped. Hydrogen bonds in the plane of the sheet - to stabalize Anti parallel and paralle. Following the protein sequence, N-->C and then N-->C the otherway.

hydrophobic interactions

The alpha-helices and beta-sheets are folded into a compact globule.

primary structure

The first level of protein structure; the specific sequence of amino acids making up a polypeptide chain.

Quaternary structure

The fourth level of protein structure; the shape resulting from the association of two or more polypeptide subunits.

Quaternary structure

The overall protein structure that results from the aggregation of these polypeptide subunits.

secondary structure

The result of hydrogen bonds between the repeating constituents of the polypeptide backbone

structural and functional features of amino acids

all 20 AA have a chiral CH that is attached to: carboxyl group amino group distinctive R exist in 2 mirror image forms: D (dextro; right) and L (levo:left) glycine has 2 identical hydrogen, no D/L, optically inacitve. D and L rotate plane polarized light in opposite direction. Proteins consist exclusively of L amino acids Cell walls (D)

Amino Acids becoming Proteins

amino acids link to one another, nucleotides attach to one another to form nucleic acids & simple sugars connect to form complex carbohydrates

Tertiary structure

_________is considered to be largely determined by the biomolecule's primary structure, or the sequence of amino acids or nucleotides

thymine

a base found in DNA (but not in RNA) and derived from pyrimidine

cytosine

a base found in DNA and RNA and derived from pyrimidine

cytosine

a base found in DNA and RNA and derived from pyrimidine; pairs with guanine

Peptide Bond

a bond that forms between the carboxyl group of one amino acid and the amino group of another. the C-N bond that forms from this is called peptide bond * water is lost in the condensation reaction, the carboxyl group of amino acids is converted to a carbonyl group in the polymer

alpha helix

a delicate coil held together by hydrogen bonding between every fourth amino acid

polypeptide bond

a long chain of amino acids

Monomer

a molecular subunit such as an amino acid, a nucleotide, or a sugar. *when bonded together, the resulting structure is called a polymer *polymerization - process of linking monomers together

uracil

a nitrogen-containing base found in RNA (but not in DNA) and derived from pyrimidine

pyrimidine

a nitrogenous base that has a single-ring structure; one of the two general categories of nitrogenous bases found in DNA and RNA; thymine, cytosine, or uracil

motif

a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance

ribose

a pentose sugar important as a component of ribonucleic acid

purines

adenine and guanine are what

Cofactors & coenzymes

cofactors -- metal ions or small organic molecules called coenzymes

alpha helix

common motif in the secondary structure of proteins

nucleotide

composed of a nucleobase (nitrogenous base), a five-carbon sugar (either ribose or 2'-deoxyribose), and one to three phosphate groups

beta turns

comprimised of 4 amino acids - connect adjacent sides of anti parallel beta sheets Type I: Contains cis Pro at position 2 (facilitates sharp turn) Type II: Contains Gly at position 3 (avoids steric clashes)

beta sheet

consist of beta strands connected laterally by at least two or three backbone hydrogen bonds

Macromolecule

denote a very large molecule that is made up of smaller molecules joined together *protein is a macromolecule

primary structure

equivalent to specifying the sequence of its monomeric subunits, e.g., the nucleotide or peptide sequence

Oligopeptide

fewer than 50 amino acids are linked together in this way *"few peptides"

deoxyribose

five-carbon sugar that is a component of DNA nucleotides

alpha helix

forming a generally twisted, pleated sheet (the most common form of regular secondary structure in proteins is the

Prions

improperly folded proteins that act as a infectious, disease-causing agent - does not differ in amino acid sequence, just their shapes are different - can induce other protein molecules to change their shape to the altered form

Quaternary structure

is a larger assembly of several protein molecules or polypeptide chains, usually called subunits in this context

alpha helix

is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier ( hydrogen bonding).

hairpin

is a special case of a turn, in which the direction of the protein backbone reverses and the flanking secondary structure elements interact. For example, a β-hairpin connects two hydrogen-bonded, antiparallel β-strands

turn

is an element of secondary structure in proteins

α-turn

is characterized by (a) hydrogen bond(s) in which the donor and acceptor residues are separated by four residues (

beta sheet

is the β hairpin, in which two antiparallel strands are linked by a short loop of two to five residues, of which one is frequently a glycine or a proline

PRIMARY STRUCTURE

linear amino acid seq AA linked by peptide bonds, cov bonds between alpha carboxyl and alpha amino groups of adjacnet residues. (lose their charges so only side chains are relativent regarding charges) peptide = less than 50 AA protein = greater than 50 AA That reaction of peptides bonds doesn't happen spontaneously Proteases doesn't need energy (breaking apart) But making it does need energy. Peptide bond has partial double bond character: Planar, rigid with regard to rotation (prevents groups from rotating) cain to be rigid. - Gives rise to cis/trans isomers - Trans preferred: Adjacent R groups positioned opposite each other -Carbons of each AA can swivel polypeptide backbone is flexible protein folding Proline can easily be cis. So proline is used to introduce sharp turns Structural element is rigid of the backbone. The onlyway to move or turn is rotate around the carbon alpha.

primary structure

linear sequence of amino acid residues, covalent bonding including disulfide bonds -SS-

beta sheet

made up of beta strands. in antiparallel, hydrogen bonding is straight across, parallel is two residues farther along the opposite chain.

secondary structure

main chain H-bonding (alpha helix, b sheet, b turn)

Competitive Inhibition

molecule competes with substrate for access to the enzyme's active site

Polypeptide

molecule that are amino acids are linked by peptide bonds into a chain *R-group orientation: makes it possible for them to interact with each other and with water *Directionality: amino group on one end of every polypeptide chain and carboxyl group on the other. N-terminus is always on left & C-terminus on right. *Flexibility: cannot peptide bond itself cannot rotate because of its double-bond nature, the single bond on either side of the peptide bond can rotate. the structure as a whole is flexible

nucleotide

monomer of nucleic acids made up of a 5-carbon sugar, a phosphate group, and a nitrogenous base

modifications of amino acid chains

post translational modifications of amino acid side chians We can sometimes have additional functional groups in amino acids. To proline and lysine, add OH (post translational modification) --> really important in collagen. If we don't have vit. C that is important for this post translational modification, then we have scurvy Adding carboxy to glutamate is vitamin k dependent and is important for calcium binding proteins (blood clotting factors)

tertiary structures

proteins assume complex, three dimensional [ ] that determine the final configuration of the polypeptide, the most important influence on this is its cellular environment - whehter its in the watery cytoplasm of a cell, in the lipids of cellular membranes or spanning a cell membrane, thus straddling two environments

adenine

purine base found in DNA and RNA; pairs with thymine in DNA and with uracil in RNA

Substrate

reactant molecules that catalysts bring to have an effective catalysts

Reactants happen when...

reactants have enough kinetic energy to reach the transition state. the kinetic energy of molecules is a function of their temperature *chemical reactions tend to proceed faster at a higher temperature *depends on both the kinetic energy of the reactants and the activation energy of the particular reaction - meaning the free energy of the transition state **kinetic energy = high = more likely for completed reactions **activation energy = high = less likely

5' to 3'

replication, transcription, and translation are carried out in this direction

five carbon sugar

ribose is a ______.

primary structure

sequence of amino acids

Physical Conditions

temperature = affects kinetic energy pH = makeup and charge of amino acids side chains *acid environments - low pH best results

amino end

the end of a protein having a free amino group

carboxyl end

the end of a protein having a free carboxyl group. The carboxyl end is encoded by the 3' end of the mRNA and is the last part of the protein to be synthesized in translation.

β-turn

the most common form) is characterized by (a) hydrogen bond(s) in which the donor and acceptor residues are separated by three residues ().

beta sheet

the second form of regular secondary structure in proteins consisting of beta strands connected laterally by five or more hydrogen bonds

primary structure

the unique sequence in which amino acids are joined

tertiary structures

three-dimensional structure