BIOC chapter 4

The α helix: Most alpha helices are

12 residues long

Short polypeptide

oligopeptide

Cysteine's R-group -CH2-SH •pKa = 8.4 therefore at physiological pH (7.4) it is

protonated

Amino acids can be classified by their chemical properties: •These classifications are made based on their

"R" groups

amino acids within the peptide are called

"amino acid residues" because only the residual atoms remain

Amino acids have 3-letter codes AND 1-letter codes.

*Most* of the time the 1-letter code is the 1st letter (a few don't) •Example: Alanine (Ala, A) however Arginine (Arg, R) b/c "A" is for alanine, we use "R" for arginine

Charge at ph 10 N-met-cys-gly-lys-glu-c

0(n)+0(met) -(cys)0(gly)+(lys)-1(glu)-(C) -2 charge

Building Blocks of Proteins:•Proteins are made up of

1 or more polypeptide chains

List the 1.) covalent and 2.)noncovalent forces that can stabilize protein structures.

1.)The primary structure is held together by covalent peptide bonds.disulfide bonds, thioester bonds, and isopeptide 2.) hydrogen bonds, ionic bonds, van der Waals interactions, zinc ions, and hydrophobic bonds.

•Most polypeptides contain

100-1000 amino acid residues

in Beta sheet, Each residue forms

2 hydrogen bonds with the neighboring strand

a single beta sheet can contain between

2 to more than 12 strands -Average = 6 strands, with 6 residues long

tertiary structure

3-d strucuture of an entire polypeptide, including all its side chains

The α helix:• ___ residues per turn of the helix, for every turn the helix rises 5.4 angstroms along its axis

3.6

Charge at ph 7 N-met-cys-gly-lys-glu-c

=+1(n)0(met) 0(cys)+0(gly)+(lys)-(glu)-(C)0 CHARGE

A polypeptide segment that has folded into a single structural unit is called a

DOMAIN •Some proteins have 1 domain, some have more!

nonpolar amino acids

Glycine, Alanine, Valine, Leucine, Isoleucine, Phenylalanine, Tryptophan, Methionine, Proline

Identify all the hydrogen bond donor and acceptor groups in the backbone.

Hydrogen bond donor: N-H(BLUE/WHITE) Hydrogen acceptor: O(RED) The α helix. In this conformation, the polypeptide backbone twists in a right-handed fashion so that hydrogen bonds (dashed lines) form between ═ and N—H (donor) groups four residues farther along. Atoms are color-coded: Cα light gray, carbonyl C dark gray, O red, N blue, side chain purple, H white.

there are Hydrophobic and Hydrophilic Residues in

Myoglobin

Compare parallel and antiparallel β sheets.

Parallel beta pleated sheets have two polypeptide strands running in the same direction while antiparallel beta pleated sheets have two polypeptide strands running in the opposite directions.

Describe the four levels of protein structure.

Primary: the sequence of amino acids forms the polypeptide chain Secondary:the primary chain forms spirals(alpha helix) and sheets(beta sheets) Tertiary: Superimposed on the secondary structure. Alpha helices and/or beta sheets are folded up to form a compact globular molecule held together by intramolecular bonds. Quaternary structure: Two or more polypeptide chains, with its own tertiary structure, combine to form a functional protein.

•In this structure, polypeptide strands are aligned and hydrogen bonding are with neighboring strands

The beta sheet

Identify the polar amino acids that are sometimes charged.

Two of the polar amino acids (glutamic acid and aspartic acid) contain carboxylic acid functional groups and are therefore acidic (negatively charged). Two of the polar amino acids (lysine and arginine) contain amino functional groups and are therefore basic (positively charged).

zinc finger

a small protein structural motif that is characterized by the coordination of one or more zinc ions in order to stabilize the fold -Only in smaller structures 20-60 residues -Zn complexes with Cys, His, Glu, and Asp tetrahedrally to help stabilize the protein

Most proteins contain

all 20 amino acids

An entire protein structure often has a mixture of some of its backbone in the

alpha helix confirmation and some in the beta sheet confirmation

3 types of secondary structure

alpha helix, beta sheet, unstructured (bturn)

Proteins are polymers of

amino acids

negatively charged amino acids

aspartate, glutamate

charged amino acids

aspartate, glutamate, lysine, arginine, and sometimes histidine

The α helix: The carbonyl oxygen forms hydrogen bond with the

backbone NH group 4 residues ahead

a secondary proteins unique properties are important for how the

backbone folds

Polar amino acids can be in

both the surface and core

Polypeptide: chain of amino acids linked together by peptide bonds

chain of amino acids linked together by peptide bonds

acidic and basic amino acids are

charged

These amino acids are also on the surface (exterior) of protein

charged amino acids

Amino acids; All but 1 of them are

chiral

Amino acids are linked via a

condensation reaction.

Dive into the 3D structure: Regular secondary structures (alpha helix, beta sheet) are typically in the

core

pH>pKa

deprotonated

Amino acid sequence is important and

dictates shape

Some polypeptide chains align in regions with

directionality.

•Ionizable groups are ones that can

either give up or gain a proton!

Dive into the 3D structure: Irregular structure (loops) are typically found on the solvent

exposed surface

Explain why biochemists know more about globular proteins than disordered proteins.

globular proteins are usually stable by themselves in aqueous solution.

methionine is not polar

has a "S" but it's surrounded by carbons on the side chain so it's mostly nonpolar

In protein secondary structure, Polypeptide (AA chain) folds in a way to maximize

hydrogen bonding

in tertiary structures: Core is almost always

hydrophobic

pH=pKa

ionized and unionized forms are equal (50%)

•Ionization state is sensitive to

local pH changes

positively charged amino acids

lysine, arginine, and sometimes histidine

•20 standard amino acids->

most proteins contain all of these

Draw a tripeptide and identify its peptide bonds, backbone, side chains, N-terminus, C-terminus, and net charge.

net charge 0

in a tertiary structure, some polar amino acids can be in the protein interior to help

neutralize their polarity

in a tertiary structure, Charged amino acids are almost always located

next to a residue with opposite charge (interact electrostatically to form an ion pair)

Explain why proteins are not rigid.

no protein exists as a completely rigid block. All proteins are inherently flexible, because individual bonds in the polypeptide chain can rotate, bend, and stretch, and secondary and tertiary structures are stabilized by relatively weak noncovalent forces. *many proteins must undergo other types of structural changes in order to carry out their biological functions.

How does a protein fold? Protein folding and protein stabilization depend on

noncovalent forces. Key factor: the hydrophobic effect

These amino acids are mostly on the INTERIOR of the protein (not exposed to solvent)

nonpolar amino acids

•Don't often participate in any chemical reactions

nonpolar amino acids

Antiparallel= chains run in

opposite directions *The NH and C=O groups of an amino acid on one strand form H bond w/ C=O and N-H groups of the opposing amino acid on the other strand

Antiparallel b sheets align in

opposite directions (hair pin).

Formation of 3D structure:Some proteins need

other proteins (molecular chaperones) to help them fold

Name some residues that are likely to be located on the protein surface and some residues that are likely to be located in its core.

outside:polar and charged ex: histidine, aspartate interior: nonpolar ex: glycine, alanine

The α helix: Side chains extend _____ and the atoms of backbone fill the inside

outward

disulfide bonds

oxidation reaction between Cysteine

in the beta sheet Polypeptide strands can be arranged in

parallel and anti-parallel confirmation

neutral polar will be

polar

•N,O, and S on the side chain can help classify an amino acid as

polar

These amino acids mostly make up the exterior of a protein but can also be found in the interior

polar amino acids -They are exposed to solvent because they are polar! (solvent= aqueous environment)

Amino acids are linked by peptide bonds to form a

polypeptide

•The different elements of secondary structure are linked together by

polypeptide loops

•essentially the AA sequence (doesn't tell anything about shape)

primary

pH<pKa

protonated

not all proteins have this, proteins that have more than 1 polypeptide, this structure defines the spatial structure of the chains

quaternary

Properties of the backbone: C-N (peptide bond) is

rigid, meaning it doesn't move

Properties of the backbone: There is some _____ about the N-Cα and Cα-C axis

rotation

Parallel b sheets align in the

same direction

Parallel = chains run in

same direction (N - C or C - N) - an amino acid on one strand connects to two amino acids on the opposing end via hydrogen bonds *dont line up perfectly

proteins fold, the confirmation of the backbone (so not the R groups) is the 20 structure.

secondary

These polypeptide loops often link

secondary structures

primary structure of protein

sequence of amino acid residues

polar amino acids

serine, threonine, tyrosine, asparagine, glutamine, cysteine

quaternary structure of a protein

spatial arrangement of polypeptide chains in a protein w/ multiple subunits

secondary structure of protein

spatial arrangement of the polypeptide backbone:

The α helix: Hydrogen bonds along the helical axis

stabilize this structure.

complete 3D confirmation including backbone AND side chains

tertiary

•Includes regular and irregular secondary structures PLUS the spatial arrangements of the R-groups

tertiary structure

the tertiary structure lets us know what happens to

the side chains

Charge of the side chains depend on

their ionization state

Explain why a globular protein has a hydrophilic surface and a hydrophobic core.

these proteins are surrounded by water molecules, so the main driving force for folding is the packing of hydrophobic side chains into the interior of the molecule, thus creating a hydropohobic core and a hydrophilic surface.

chiral

they are asymmetric, non-superimposable, "left" and "right" handed

Overall factors that affect protein stability

•Hydrogen bonding (within the secondary structure) •Ion pairing (minimal effects) •Disulfide bonds (between cysteines) •Interaction with Zn ions (Zinc Fingers)

backbone of protein

•The backbone is planar (not including R groups, because they are not planar)

Proteins

•The workhorses of the cell •This chapter (Ch4) we will focus on their structure, next chapter will focus on their function