Protein Structures

Question 1

What is the difference between positive and negative sense RNA?

Answer 1

Positive-sense viral RNA is similar to mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation

Question 2

What does 1HHO stand for?

Answer 2

Human Hemoglobin

Question 3

What type of pKa does the carboxyl group have and what happens at ~7pH?

Answer 3

COOH/Coo- has low pKa ~2
Tends to deprotonate and become negatively charged at physiological pH

Question 4

What type of pKa does the amino group have and what happens at ~7pH?

Answer 4

NH2/NH3+ has a high pKa ~9-10
Tends to protonate and become positively charged at physiological pH

Question 5

What is a chiral center?

Answer 5

An atom that has 4 different groups bonded to it in such a manner that it has a non-superimposable mirror image

Question 6

Define enantiomer

Answer 6

Aka stereoisomer have the same molecular formula and sequence of bonded atoms but differ in the way the atoms are arranged in space

Question 7

What are the two enantiomers for each amino acid, and which is more common?

Answer 7

D and L forms

In proteins, the L form is predominantly used

Question 8

What are the exceptions, where L-amino acids is not used?

Answer 8

Non-ribosomal system uses D-amino acid (Microbial peptides)
Post translational enzymatic conversion of L to D (Euk peptides/proteins)

Question 9

What are the polar side chains?

Answer 9

Chains charged at pH7 or groups that can H bond
OH
SH
CO-NH (amide)
NH
COOH

Question 10

What are the non-polar side chains?

Answer 10

Alkyl hydrophobic groups which cannot H bond

C-H
C-C
C-S-C

Question 11

Describe electronegativities of atoms in non-polar groups

Answer 11

Low electronegativities = low difference

Question 12

Define amphipathic

Answer 12

A molecular having both hydrophilic and hydrophobic

Question 13

What are the two amphipathic amino acids?

Answer 13

Tryptophan and methionine = non-polar side chain

Question 14

What are the 6 hydrophobic amino acids?

Answer 14

Alanine + Phenylalanine
Proline
Valine
Leucine + Isoleucine

All non-polar side chains

Question 15

What is the charge of glycine?

Answer 15

Neutral
So counts as a non-polar side chain

Question 16

Which amino acids with polar side-chains are amphipathic?

Answer 16

Threonine
Tyrosine
Lysine

Question 17

Which amino acids with polar size chains are basic?

Answer 17

Arginine
Lysine
Histidine

Question 18

Which amino acids with polar side chains are acidic?

Answer 18

Aspartate
Glutamate

Question 19

Where are non-polar and polar amino acids found in a channel?

Answer 19

Non-polar tend to be located on the surface in contact with the membrane

Polar will line interior pores to great hydrophilic channels

Question 20

What functions do serine & threonine do?

Answer 20

Phosphorylation
Glycosylation
Deprotonation -> nucleophilic catalysis

Question 21

What are the 3 roles of cysteine and why?

Answer 21

1. Nucleophilic catalysis
2. Metal coordination
3. S-S bonds

The first two because S has more shells than O/N so electrons are held weakly. This means Cys has a low pKa(8.6) so deprotonates.

Question 22

What are engineered disulphide bonds used for?

Answer 22

To stabilize or eliminate protein dynamics

Question 23

What bonding does Asparagine perform?

Answer 23

N-linked glycosylation

Question 24

How is SARS-CoV-2 affected by varying pH?

Answer 24

Virus particles are assembled in their low pH vesicles
Once the virus makes contact with neutral pH outside the cell, the spike protein changes from closed conformation to open conformation

Important the timing it right, premature opening can cause spike protein to decay too early

Question 25

Name the 3 aromatic amino acids

Answer 25

Phenylalanine Tyrosine Tryptophan

Question 26

What are the two interactions aromatic amino acids do?

Answer 26

Pi-Pi interactions Cation-Pi interactions

Question 27

What property does glycine give proteins?

Answer 27

Flexibility

Question 28

What property does proline give proteins?

Answer 28

Rigidity because of its very rigid side chains

Question 29

What property does methionine give proteins?

Answer 29

Ability to participate in enzymatic metal catalysis

Question 30

What property do aromatic amino acids give proteins?

Answer 30

Form gates in ion channels & transporters UV light absorptions Ligand binding via non-covalent interactions

Question 31

What property does tyrosine give proteins?

Answer 31

Regulation of protein and cellular functions via phosphorylation Facilitates protein secretion, viral entry into cells & metal binding via sulfation

Question 32

What property does tryptophan have?

Answer 32

Largest side chain of all amino acids Low frequency in proteins Participates in electron transport (aromatic) Fluorescent

Question 33

Define amino acid residues

Answer 33

Amino acids in the peptide bond/chain

Question 34

Define resonance and what role it plays in peptide bond

Answer 34

Resonance = delocalization of electron within a molecule Resonance stabilizes the peptide bond

Question 35

What type of bond is a peptide bond?

Answer 35

Partial double bond

Question 36

Which conformation do peptide groups more commonly assume, and why?

Answer 36

Trans conformation = partly due to steric interference Cis conformation is less stable than trans

Question 37

----- Secondary structure -----

Question 38

What restricts rotation freedom of a peptide bond?

Answer 38

Rotations around backbone bonds Atomic steric clashes

Question 39

What atoms are in a Phi bond?

Answer 39

Cα-N

Question 40

What atoms are in a Psi bond?

Answer 40

Cα-C

Question 41

What conformation does a Phi angle of 0 make?

Answer 41

Cis conformation N-H and Cα-R point in the same direction So 180 degree angle = trans

Question 42

What is a Ramachandram diagram used for?

Answer 42

Plot sterically favourable combinations of Phi and Psi angles = to predict preferred secondary structures

Question 43

What are the exception in a Ramachandran diagram and why?

Answer 43

Glycine = has more regions because more flexible Proline = has fewer regions because geometrically limited

Question 44

What is the pattern in a right-handed α-helix?

Answer 44

Carbonyl O of x amino acid H bonds with amid H of x+4 amino acid

Question 45

RH α-helix radius?

Answer 45

~2.3 angstrom

Question 46

RH α-helix residues per turn?

Answer 46

3.6 (5.4 angstrom)

Question 47

RH α-helix phi and psi angles

Answer 47

-57 -47

Question 48

In globular proteins, what % of resides are in RH α-helix?

Answer 48

~30%

Question 49

Top 5 residues in α-helices and why?

Answer 49

M = methionine A = alanine R = arginine K = lysine L = leucine Short side chains = produce less steric clashes

Question 50

Unfavourable residues in α-helices, and why?

Answer 50

Proline is a helix breaker cuz rigid Glycine is too flexible Polar side chains = Ser, Aspartate & Asparagine Might form H bonds with backbone other than amide H Beta-branch side chains = Thr, Val, Isoleucine Favoured in beta-sheets because of branching

Question 51

Proline substitution in vaccine development

Answer 51

Proline’s rigid cyclic structure restricts flexibility locking it in a specific confirmation This stabilises the prefusion confirmation of the antigen for vaccines Reduces chances of proteins changing shape so makes vaccines more effective and safe

Question 52

Where is 3-10 helix found?

Answer 52

As a single turn at the beginning or end of α-helices (3% of proteins)

Question 53

Role of 3-10 helix?

Answer 53

Connecting secondary elements & fixing distortions formed within α-helix (by Proline***)

Question 54

Which is the tighter helix?

Answer 54

3-10 is tighter than α-helix With 3.0 resides per turn instead of 3.6

Question 55

What type of β-strand are there?

Answer 55

Parallel and antiparallel

Question 56

Do β-strands appear in proteins?

Answer 56

No normally in their isolated form = they arrange into β-sheet

Question 57

In globular proteins, what % are β-sheets?

Answer 57

~20%

Question 58

Name 3 structural motifs using beta sheets

Answer 58

β-a-β motif Twisted β-sheet (thioredoxin) β-barrel

Question 59

What is the function of helices & sheets?

Answer 59

Compaction of polypeptide chain = keeps proteins soluble in dense cytoplasm Reduce the cost of burying polar backbone groups = pair polar groups efficiently

Question 60

How does burying a peptide bond work? ***

Question 61

What is the function of β-turn(reverse turn) structure?

Answer 61

Usually connects anti-parallel b-strands Allows peptide chain to reverse direction

Question 62

What is the difference between type I and type II β-turn?

Answer 62

Different dihedral angles

Question 63

Describe the bonding in beta-turn (reverse turn) structure

Answer 63

Carbonyl O (i ) is H bonded to Amide H of residue i + 3

Question 64

What amino acids are most commonly found in reverse-turns?

Answer 64

Proline because of cyclic structure Glycine because most sterically flexible Both accommodate a kink