Biochem 5

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Hydrophobic interactions-electrostatic interactions-hydrogen bonds-covalent bonds

...

__ has had a profound effect on the structural and fictional properties of biomeolcules

Chirality -Right-handd helices observed in proteins result form the exclusive presence of L- amino acids. Chiral molecules- most bind substrate molecules in only one enantiomeric form.

These can help stabilize many polypeptides and proteins

Disulfide bridges

These promote the correct refolding of damaged proteins

heat shock proteins (hsps)

Polypeptides that have similar amino acid sequences and have arisen from same ancestral gene are said to be __ Sequence comparisons among homologous polypeptides have been used to trace the genetic relationship of different species(cytochrome C- mitochondria)

homologous

It has also become increasingly clear that the folding and targeting of many proteins in living cells are aided by a group of molecules now referred to as

molecular chaperones(found in bacteria to higher animals/plants) mitochondria, chloroplasts, ER

Globular proteins are compact because of efficient packing as the polypeptide folds. During this process...

most water molecules are excluded from proteins interior, making interactions between polar/nonpolar groups possible

mygobloin gives up oxygen only when

muscle cell's oxygen concentration is very low. Has a greater affinity for o2 than does hemoglobin

B-pleated sheets are either

parellel or antiparallel.

As the polypeptide chain folds, it forms certain localized arrangements of adjacent amino acids that constitute the

secondary structure

The folding of larger polypeptides typically involves

the formation of several intermediates.

These are compact spherical molecules that are usually water soluble. Typically have dynamic functions

Globular Proteins(hemoglobin and albumin)

A number of eukaryotic proteins, reffered to as ____, contain numerous duplicate or imperfect copies of one or more domains that are linked in a series

Modular--mosaic proteins

Type of spectroscopy in which relationship between molecular motion and structure is probed with eletromagnetic radiation

circular dichroism.

The overall three-dimensiona shape that a polypeptide assumes is called

Tertiary structure.

This refers to nonarmatic hydrocarbons such as methane and cyclohexane.

aliphatic

Ligand-induced conformational changes in such proteins are called. What triggers them and what are they called The kind of reaction

allosteric transitions, and the ligands that trigger then are called effectors/modulators. * Allosteric effects can be +/-, depending on whether effector binding increase or decreases the proteins affinity for other ligands.

The hydrolysis of each polypeptide yields a set of amino acids , referred to as the molecules

amino acid composition

The interactions between ___ determine the protein's three dimensional structure and its functional role and relationship to other proteins

amino acid residues

Two types of hydrocarbon side chains are found in non polar.

aromatic and aliphatic

Examples of structural support in regards to protein

collagen(major components of connective tissue), fibroin (silk protein) movement - tubulin-actin

As the first o2 binds to hemoglobin, the binding of additonal o2 to the same molecule is enchained.

cooperative binding

Large globular proteins often contain several compact units called

domains. Typically structurally independent segments that have specific functions (binding an ion small molecule).

These aspects of organic molecules determine which reactions they may undergo

Functional groups.

These standard amino acids have side chains with carboxylate groups

Acidic Amino Acids. Negatively charged

The ___ is a rigid, rodlike structure that forms when a polypeptide chain twists into a right-handed helical conformation. Hydrogen bonds form between the N-H group of each amino acid and the carbonyl group of the amino acid four resides away - Some amino acids do not foster alpha helical formation, why?

Alpha -helix -Peptide bonds, allowed limits on the o/ v/ angles. Amino acid sequences with a large number of charged amino acids and bulky R groups, are incompatible with alpha helix structures. Alpha bonds are crucial in alpha helix structure.

In these, these bonds are arranged in opposite directions

Antiparallel

These hydrocarbons containing cyclic structures that constitute a class of unsaturated hydrocarbons with unique properties.

Aromatic

These form when two or more polypetide chain segments line up side by side composition?

B pleated sheets. Each segment is referred to as beta-strand. Each is fully extended not coiled. Stabilized by hydrogen bonds that form between polypeptide backbone n-h and carbonyl groups of adjacent chains.

These amino acids bear a positive charged at physiological ph. They can therefore form Ionic bonds with acidic amino acids

Basic Amino acids.

A significant number of primary sequence changes do not affect a polypeptide's function. Some of these subsitutions are said to be___ because an amino acid with a chemically similar side chain is substituted. Some sequence positions are significantly less stringent. These residues, referred to as variable, apparently perform nonspecific roles in the polypeptide's function Substitutions at either sites have been used to _____ Quite often overall 3d structure does not change despite numerous amino acid sequences.

Conservative Variable Trace evolutionary relationships)Longer the time since two species diverged, larger number of differences in certain polypeptide's primary structure", supported by cytochrome C primary sequence in chimps/humans Whales,sheep, differ by 10 residues from the human protein. 50 million years ago

These are long, rod-shaped molecules that are insoluble in water and physically tough. Found in skin, hair and nails (keratins). Structural and protective functions

Fibrous Proteins

Two major molecular chaperone classes

HSP70-Hsp60s

Each type of polypeptide folds into its own unique and functional conformation. Over time, however, as the result of evolutionary processes, the amino acid sequences of polypeptides change owing to the random and spontaneous alterations in DNA sequences called

Mutations

In these, B-pleated sheet structures, the hydrogen bonds in polypeptide chains are arranged in the same direction

Parallel

These amino acids have functional groups capable of hydrogen bonding, they easily interact with water.

Polar amino acids (hydrophilic)

Molecules such as amino acids that posses primary amine groups can reversibly react with carbonyl groups. The imine products of this reaction are often referred to as

Schiff bases.

Most asymmetrical molecules found in living organisms occur in only one

Stereoisomeric form, either D or L. Few exceptions, only L- amino acids are found in proteins.

Molecules that bear both positive and negative charges on different atoms are called The ___, however, gives each amino acid its unique properties

Zwitterions The R group

Forces that drive folding process

bond rotations ,free energy considerations, behavior of amino acids in aqueous environments

Once the carboxyl group has lost its proton, alanine has no net charge and is electrically neutral. THe ph at which this occurs wis called the When amino acids are incorporated in polypeptides, the alpha amino and alpha carboxyl groups

isoelectric point (pI). PI= Pk1 + Pk2 -------- 2 Lose their charges( all ionzable groups of proteins are side chain groups of seven amino acids histidine, lysine, arginine, aspartate, glutamate, cystenine and tyrosine. -pka values of individual R groups are affected by their positions within protein microenviroments.

The structure of BAB unit consists of The b-turn is common in proteins rich in

two parallel B-pleated sheets are connected by alpha helix segment. Stabilized by hydrophobic interactions between non-polar side chains projecting from interacting surfaces of t each aspect (a/b) alpha-helical segments

Denaturation tempreature

vibration increases, , interactions are disrupted, protein unfolds. Can use in purification procedures, some more resistant

Amino acid can behave as either an acid or a base

Amphoteric.

Denaturation- strong acids bases

Changes in ph result in pronation of some side chain groups. Alters hydrogen bonding and salt bridges. Reaches isolectric point= may precipitate from solution.

The ___ are a family of molecular chaperones that bind to and stabilize proteins during the early stages of folding. numerous __monomers bind to short hydrophobic segments in unfolded polypeptides thereby preventing molten globule formation. Each type posses two binding sites, one for an unfolded protein segment and another for ATP. Release of polypeptide from this involves ATP hydrolysis. Mito-ER localized variables required for transmembrane translocation of some polypeptides.

HSP70

Substances released from one nerve cell that influences the function of a second nerve cell or a muscle cell Chemical signal molecules produced in one cell that regulate the function of other cell -Amino acids are precursors of a variety of complex nitrogen-containing molecules. Nitrogenous base components of nucleotides and nucleic acids, heme and h chlorophyll.

Neurotransmitters hormones

Amino acids are classified according to their capacity to interact with water. 4 classes

Nonpolar--polar--acidic--basic

These play an important role in maintaining the three dimensional structures of proteins,

Nonpolar. They interact poorly with water

These amino acids consist of amino acid residues that have been chemically modified after incorporation into a polypeptide or amino acids that occur in living organisms but are not found in proteins

Nonstandard amino acids

Serine, Threonine, Tyrosine, Asparagine, and Glutamine belong to this category Serine, threonine, and tyrosine contain a

Polar amino acids. polar hydroxyl group.

The amino acid sequence, is specified by genetic information

Primary structure

The exception, __, differs from the other standard amino acids in that its amino group is secondary, formed by ring closure between the R group and the amino nitrogen.

Proline

These are composed of protein molecules that are related by amino acid sequence similarity Proteins that are more distantly related are classified into

Protein families. Common ancestry. superfamilies

A process in which unorganized (newly synthesized) molecule acquires a highly organized structure, occurs as consequence of interactions between side chains in their primary structure

Protein folding

Denaturation- detergents

Substances that disrupt hydrophobic interactions ,causing proteins to unfold into extended polypeptide chains. These molecules are called amphibpahtic (both ilic)

Many globular proteins contain combinations of alpha helix and beta pleated sheet secondary structures. These patterns are called

Supersecondary structures or motifs.

3d- Reason for occurrence of multisubunit proteins (3)

Synthesis of separate subunits may be more efficient than increasing length of single polypeptide chain. -replacement of smaller, worn out components can be managed more effectively(collagen) -Complex interactions of multiple subunits help regulate a protein's biological function

Denaturtion- reducing agents

Urea, reducing events convert disulfide bridges i to sulfhydrl groups. Disrupts hydrogen bonds and hydrophiv interactions

Denauration organic solvents

Water soluble organic solvents (enthanol) interfere with hydrophobic interactions because they interact with non polar R groups, form hydrogen bonds. Non polar solvents also disrupt hydrophobic interactions

The most important examples of schiff base formation in biochemistry occur in amino acid metabolism. Schiff bases, referred to as ___, formed by reversible reaction of an amino group with an aldehye group, are intermediates in transamination reactions

aldimines

Two aldehydes from an a, b-unsatured aldehyde linkage

aldol condensation

The most commonly observed types of secondary structure are the What influences o/ V/ angles?

alpha-helix and the beta-pleated sheet. Stabilized by localized hydrogen bonding between carbonyl and N-H groups in polypeptide's backbone peptide bonds are rigid, alpha carbons are swivel points for polypeptide chain. Several properties of R groups (size/charge) attached to alpha carbon influence the angle. Certain amino acids foster or inhibit specific secondary structures. Most fibrous proteins are composed almost entirely of secondary structural patterns.

Phenylalaine and Tryptophan contain Glycine, alanine, valine, leucine, isoleucine, proline A ___ appears in the aliphatic side chains of methionine and cysteine

aromatic rings Have aliphatic R groups. Sulfer atom

Because the alpha carbons of 19/20 standard amino acids are attached to for different groups, they are referred to as Molecules with chiral carbons can exist as ___, molecules that differ only in spatial arrangement of their atoms. These two isomers are mirror images of each other. Such molecules are called ___, cannot be superimposed on each other

asymmetric, or chiral, carbons Stereoisomers Enantiomers( identical physical properties, except they rotate plane-polarized light in opposite directions. Optical isomers

3d- covalent linkages are created by What are the most prominent covalent bonds in tertiary structure? benefits? What lacks these features

chemical reactions that alter a polypeptide's structure during of after its synthesis. The most prominent covalent bonds in tertiary structure ate the disulfide bridges found in many extracellular proteins. Protect protein from adverse changes in PH. Intercellular proteins do not contain disulfide bridges because of high cytoplasmic concentrations of reducing agents.

The assembly of collagen fibers in their extracellular locations, such as tendons and bone

fibrilogenesis

3d - dynamic hydration shell that forms around a protein, also contributes to the

flexibility required for biological activity

The core-three -dimensional structure of a domain is called a Domains are classified on the basis of their

fold core motif structure Alpha domains = alpha helices and B-domains consists of anti parallel B strands a/b domains- various combinations of a helix alternating with b strands A+B domains are primarily B - sheets with one or more outlying alpha helices Most proteins contain two or more domains

The biological functions of ___usually involve precise binding of small ligands, or large macromolecules such as nucleic acids or other proteins.

globular proteins

Fibrous proteins typically contain Keratin- silk fibronin

high proportions of secondary structures, such as alpha helices, or b-pleated sheets. Rod like sheet like shapes. Have structural rather than dynamic roles. Keratin(bundles of alpha helices) Fibroin antiparallel b-pleated sheets.

Once an unfolded polypeptide has been released by ___, it is passed on to a member of a family of molecular chaperones referred to as ____, which mediate protein folding. These form a large structure composed of two stacked seven-ssubunit rings. The unfolded protein enters the hydrophobic cavity of the hsp60 complex. When folding is complete, ATP hydrolysis converts the cavity to a hydrophilic surface and the folded protein domain moves out of the cavity. When the cavity is empty, it reverts to the hdroyphbic surface in which form it can accept ATP and an unfolded protein for a repeat of the cycle.

hsp70-hsp60s

The nonpolar amino acids contain mostly

hydrocarbon R grops that do not bear a charge.

The strongest electrostatic interaction in proteins occur s between

ionic groups of opposite charge.. Salt bridges, nonequivalent bonds are significant only in regions of the protein where water is excluded because of the energy required to remove water molecules from ionic groups near surface.

The stabilization contributed by small structural water molecules may free polypeptide from some of its internal interactions. The resulting increased flexibility of polypeptide chain is believed to play a critical role in the binding of molecules called

ligands

Neduatartion metals

mercury, lead, a disrupt salt bridges by forming ionic bonds with negatively charged groups., bond with sulfhydryl groups, result in significant change in structure/function

Sickle-celll anemia

molecule diseases HbA Human adult hemoglobin, composed of two identical alpha chains and 2 identical beta chains. Sickle-cell results form a single amino acid substitutions in the beta chain of HbA. substitutions of a hydrophobic valine for a negatively charged gluatmic acid. Aggregate to form rigid rodlike structures in oxygen free state, susceptible to hemolysis

The term___ refers to a partially organized globular state of a folding polypeptide that resembles the molecules' native state.

molten globule. Within the interior of a molten globule, tertiary interactions among amino acid side chains are fluctuating; that is, they have not yet stabilized.

Proteins have multiple and often unreleated functions These are heat shock proteins that protect cells from physiological stress

multifunction proteins alpha Crystallins

IF there is a complete lack of ordered structure, the term

natively unfolded proteins. Most unstructured proteins are eukaryotic. Folding of IUPs into stable 3d, is prevented by biased amino acid sequences that have polar/charged amino acids. * diversity of functions. Many are involved in regulated of signal transduction, transcription, translation, cell proliferation

Polypeptide subunits assemble and are held together by

non-covalent interactions such as the hydrophobic effect, electrostatic interactions and hydrogen bonds.

3D- Multisubunit proteins in which come of all subunits are identical are referred to as

oligomers. They are composed of promoters. *large number of oligomeric proteins contain two or four subunit promoters, referred to as dimers and tetramers, respectively.

dissociation of oxygen from hemoglobin is enchanted if

ph decreases, Bohr effect.

These are linear polymers composed of amino acids linked together by peptide bonds These are amide linkages formed when the unshared electron pair of the alpha amino nitrogen atom of one amino acid attacks the alpha carboxyl carbon of another in a nucleophilic acyl substituion reaction The type of reaction for peptide bond formation Linked amino acids are referred to as When two amino acids are linked--

polypeptide. peptide bonds dehydration, water molecule is removed. amino acid residues dipeptide

Tertiary- presence of water

precludes the formation of hydrogen bonds with other species

Conjugated proteins are classified according to the nature of their

prosthetic groups. Glycoproteins contain carbohydrate component. lipoproteins contain lipid molecules.

Proteins that consists of two or more polypeptide chains are said to have a quaternary structure

quaternary structure

Characterized the peptide bond as

rigid and plana( flat). C-N bonds are shorter than normal C-N bonds. Partial double b-bond character. Rigidity of peptide has consequences- bonds in polypeptide backbone cannot rotate freely, limits on number of conformational possibilities.

The __ determines the final three-dimensional configuration of each protein

sequence of amino acids.

Because of their diversity, proteins are often classified in two additional ways

shape and composition Proteins are classified into two major groups based on their shape, Fibrous proteins and Globular Proteins.

On the basis of composition, proteins are classified as either These proteins contain only amino acids. These proteins consist of a simple protein combined with a non protein component. The non protein component is called A protein without its prosthetic group is called an A protein molecule combined with its prosthetic group is refered to as a

simple and conjugated Simple proteins Conjugated--Prosthetic group--apoprotein--holoprotein

Is a recomindant Dna tecniqque i which specific sequence changes can be introduced in to a predetermined position in cloned genes

site-directed mutagensis ( revealed that protein folding is a step wise processes in which secondary structure formations appear to be an importance force infolding) Showed that amino acid subsitutions reveled that changes in surface amino acids rarely affect protein's structure subsituional of amino acids within hydrophobic core often lead to serious changes Folding is not a random processed based on primary sequence, also too complex, of protein folding *numerous routes that polypeptide can take to forld into native state.. Low energy state

Denautration- salt concentration

some h2o interact with izoniable grops are attracted rto salt ions. Solvent molecules available to interact decreases, protein-protein interaction sin crease. Solvation spheres surrounding protein io ionized groups are removed. Protein precipitates. Salting out(process) Usually reversible, used in protein purification

Every polypeptide has a

specific amino acid sequence.

The 20 amino acids that are commonly found in naturally occurring polypeptides are referred to as

standard amino acids.

In proteins that consists of more then one polypeptide chain, each polypeptide is a called a

subunit. Ligand-binding pockets are water-depleted regions of the protein.

Note that 19 of the standard amino acids have

the same general structure.

Folding of proteins is As polypeptide folds, favorable (negative ) H values are the result in part of the sequestration of hydrophobic side chains within the interior of the molecule and the optimization of other non covalent interactions. Opposing these factors is the unfavorable decrease in entropy that occurs as the disorganized polypeptide folds into its highly organized native state. The change in entropy of the water that surrounds the protein is positive because of the decreased organization of the water in going from the unfolded to the folded state of protein. * the precarious balance between favorable and unfavorable forces allow proteins the flexibility they require for biological function

thermodynamically favorable (-g)

Collagen is composed of

three left-handed polypeptide helices that are twisted around each-other to form a right-handed cripple helix.