Week 1: Primary Level of Protein Structure

Question 1

What are the pKas of COOH and amino groups?

Answer 1

2 and 10

Question 2

What is a zwitterion?

Answer 2

At neutral pH the carboxylic acid will be deprotonated and amino group will be protonated

Question 3

What hybridization is the alpha carbon for all amino acids? What geometry?

Answer 3

sp3, tetrahedral geometry

Question 4

Which form do all amino acids exist in body? What are the 2 consequences of this?

Answer 4

L. 1) surface of any protein is asymmetric - basis for highly specific molecular recognition of binding targets. 2)promotes formation of secondary structures.

Question 5

Which two amino acids have an additional stereocenter at the beta carbon?

Answer 5

Isoleucine and threonine

Question 6

What is a peptide bond?

Answer 6

Amino acids link together via amide bonds between the alpha carboxylic acid group on one and alpha-amino group on another - peptide bond and products are peptides.

Question 7

Which end are amino acids added to?

Answer 7

C-terminal

Question 8

What is a portion of an amino acid without water? What suffix do they get?

Answer 8

Amino acid residue, gets suffix -yl.

Question 9

What does the partial double bond character of peptide bonds mean? (see images)

Answer 9

Peptide bonds have partial double bond character: there is no free rotation about the peptide bond (w), the two alpha carbons are usually trans and the six backbone atoms (C, C, C, O, N, H are coplanar). Rotations around the phi and psi are possible but may be sterically hindered by side chain steric clash.
Most possible angles of phi and psi are impossible due to the clashes.

Question 10

How do you find what combinations of psi and phi are allowed? (see images)

Answer 10

1. Hold psi at fixed angle. 2. rotate phi through given angle. If steric clash occurs, this combination is not allowed. 3. Rotate phi a bit more, repeat step 2. 4. Change the angle of psi and repeat 2-4.

Question 11

What is a Ramachandran plot? See images

Answer 11

map of all theoretically possible combinations of phi and psi angles on which are in yellow - those combinations that are sterically permitted and green, those actually found in proteins.

Question 12

Where are psi and phi found?

Answer 12

Psi - between alpha carbon and carboxyl carbon

Phi - between alpha carbon and amide.

Question 13

What two conformations can peptide bonds be? Which is favoured? When is the other favoured instead?

Answer 13

Can be trans or cis. Trans is favored because R groups on adjacent alpha carbons can interfere in cis. Except in sequence X-Pro where cis is sometimes favoured.

Question 14

Describe the resonance hybrids of peptide bonds. (see images)

Answer 14

Double bond on oxygen, or double bond with nitrogen.

Question 15

What is an oligopeptide?

Answer 15

Chains with only a few amino acid residues

Question 16

What is a polypeptide?

Answer 16

Chains with 15-20 residues

Question 17

What is a protein?

Answer 17

Chain greater than 50 residues

Question 18

Are the amino and carboxylic acid ends reactive in oligopeptides and polypeps?

Answer 18

Most are unreacted with exception of rings.

Question 19

How do you write polypeptide sequences?

Answer 19

N-terminus -> C-terminus

Question 20

What is a conservative mutation to a protein? Non-conservative?

Answer 20

Conservative - conserve chemical properties and/or size of chain or nonconservative.

Question 21

What did Pauling and Corey discover?

Answer 21

Linus Pauling and R.B Corey, understanding of hydrogen bond and knowledge of amino acid structures led to their prediction as the alpha helix and beta sheet as underlying structural elements of proteins.

Question 22

What is an alpha helix? How many residues per turn? What is translation per residue? What is the helix pitch?

Answer 22

H-bonds are co-linear with chain direction, they form between residue n and n+4. Residue n provides backbone (C=O - h bond acceptor) and residue n+4 provides backbone N-H (h-bond donor).

Are 3.6 residues per turn. The translation is 1.5 amperes per residue. Helix pitch = 5.4 amperes per turn

Question 23

What is beta sheet? Describe parallel vs. antiparallel

Answer 23

Each strand is nearly flat, each residue is flipped by 180 degrees relative to neighbour. Backbone H-bonds are at nearly right angles to chain direction. Always has 2+ strands.

Parallel strands have flatter extended sheets and antiparallel have a slight twist and can form barrel-like structures.

Question 24

What polypeptide starts translation?

Answer 24

N-formylmethionine (prokaryotes and eukaryotic organelles) and methionine (in eukaryotes) at N-terminal position.

Question 25

What are the stop codons?

Answer 25

UGA, UAA, UAG

Question 26

What is the start codon?

Answer 26

AUG

Question 27

What is sequence identity and similarity?

Answer 27

distinguish sequence identity from sequence similarity - match amino acids. Sequence similarity is based on finding best alignment of sequences compared. Can score high, medium or low.

Question 28

What does it mean if two aligned protein sequence share at least 25% amino acid sequence?

Answer 28

They will have similar structure and likely function.

Question 29

What does it mean if protein sequences are homologous?

Answer 29

Protein sequences are homologous were any sequence similarity is though to be result of common evolutionary ancestry. Greater degree of protein sequence similarity = closer evolutionary relationship.

Question 30

What can be determined when several homologous protein sequences are aligned?

Answer 30

Consensus sequence, can be represented by sequence logo to show degree of amino acid conservation.