Protein Structures Flashcards
What is the difference between positive and negative sense RNA?
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
What does 1HHO stand for?
Human Hemoglobin
What type of pKa does the carboxyl group have and what happens at ~7pH?
COOH/Coo- has low pKa ~2
Tends to deprotonate and become negatively charged at physiological pH
What type of pKa does the amino group have and what happens at ~7pH?
NH2/NH3+ has a high pKa ~9-10
Tends to protonate and become positively charged at physiological pH
What is a chiral center?
An atom that has 4 different groups bonded to it in such a manner that it has a non-superimposable mirror image
Define enantiomer
Aka stereoisomer have the same molecular formula and sequence of bonded atoms but differ in the way the atoms are arranged in space
What are the two enantiomers for each amino acid, and which is more common?
D and L forms
In proteins, the L form is predominantly used
What are the exceptions, where L-amino acids is not used?
Non-ribosomal system uses D-amino acid (Microbial peptides)
Post translational enzymatic conversion of L to D (Euk peptides/proteins)
What are the polar side chains?
Chains charged at pH7 or groups that can H bond
OH
SH
CO-NH (amide)
NH
COOH
What are the non-polar side chains?
Alkyl hydrophobic groups which cannot H bond
C-H
C-C
C-S-C
Describe electronegativities of atoms in non-polar groups
Low electronegativities = low difference
Define amphipathic
A molecular having both hydrophilic and hydrophobic
What are the two amphipathic amino acids?
Tryptophan and methionine = non-polar side chain
What are the 6 hydrophobic amino acids?
Alanine + Phenylalanine
Proline
Valine
Leucine + Isoleucine
All non-polar side chains
What is the charge of glycine?
Neutral
So counts as a non-polar side chain
Which amino acids with polar side-chains are amphipathic?
Threonine
Tyrosine
Lysine
Which amino acids with polar size chains are basic?
Arginine
Lysine
Histidine
Which amino acids with polar side chains are acidic?
Aspartate
Glutamate
Where are non-polar and polar amino acids found in a channel?
Non-polar tend to be located on the surface in contact with the membrane
Polar will line interior pores to great hydrophilic channels
What functions do serine & threonine do?
Phosphorylation
Glycosylation
Deprotonation -> nucleophilic catalysis
What are the 3 roles of cysteine and why?
- Nucleophilic catalysis
- Metal coordination
- 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.
What are engineered disulphide bonds used for?
To stabilize or eliminate protein dynamics
What bonding does Asparagine perform?
N-linked glycosylation
How is SARS-CoV-2 affected by varying pH?
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
Name the 3 aromatic amino acids
Phenylalanine
Tyrosine
Tryptophan
What are the two interactions aromatic amino acids do?
Pi-Pi interactions
Cation-Pi interactions
What property does glycine give proteins?
Flexibility
What property does proline give proteins?
Rigidity because of its very rigid side chains
What property does methionine give proteins?
Ability to participate in enzymatic metal catalysis
What property do aromatic amino acids give proteins?
Form gates in ion channels & transporters
UV light absorptions
Ligand binding via non-covalent interactions
What property does tyrosine give proteins?
Regulation of protein and cellular functions via phosphorylation
Facilitates protein secretion, viral entry into cells & metal binding via sulfation
What property does tryptophan have?
Largest side chain of all amino acids
Low frequency in proteins
Participates in electron transport (aromatic)
Fluorescent
Define amino acid residues
Amino acids in the peptide bond/chain
Define resonance and what role it plays in peptide bond
Resonance = delocalization of electron within a molecule
Resonance stabilizes the peptide bond
What type of bond is a peptide bond?
Partial double bond
Which conformation do peptide groups more commonly assume, and why?
Trans conformation = partly due to steric interference
Cis conformation is less stable than trans
—– Secondary structure —–
What restricts rotation freedom of a peptide bond?
Rotations around backbone bonds
Atomic steric clashes
What atoms are in a Phi bond?
Cα-N
What atoms are in a Psi bond?
Cα-C
What conformation does a Phi angle of 0 make?
Cis conformation
N-H and Cα-R point in the same direction
So 180 degree angle = trans
What is a Ramachandram diagram used for?
Plot sterically favourable combinations of Phi and Psi angles = to predict preferred secondary structures
What are the exception in a Ramachandran diagram and why?
Glycine = has more regions because more flexible
Proline = has fewer regions because geometrically limited
What is the pattern in a right-handed α-helix?
Carbonyl O of x amino acid
H bonds with amid H of x+4 amino acid
RH α-helix radius?
~2.3 angstrom
RH α-helix residues per turn?
3.6 (5.4 angstrom)
RH α-helix phi and psi angles
-57
-47
In globular proteins, what % of resides are in RH α-helix?
~30%
Top 5 residues in α-helices and why?
M = methionine
A = alanine
R = arginine
K = lysine
L = leucine
Short side chains = produce less steric clashes
Unfavourable residues in α-helices, and why?
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
Proline substitution in vaccine development
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
Where is 3-10 helix found?
As a single turn at the beginning or end of α-helices (3% of proteins)
Role of 3-10 helix?
Connecting secondary elements & fixing distortions formed within α-helix (by Proline***)
Which is the tighter helix?
3-10 is tighter than α-helix
With 3.0 resides per turn instead of 3.6
What type of β-strand are there?
Parallel and antiparallel
Do β-strands appear in proteins?
No normally in their isolated form = they arrange into β-sheet
In globular proteins, what % are β-sheets?
~20%
Name 3 structural motifs using beta sheets
β-a-β motif
Twisted β-sheet (thioredoxin)
β-barrel
What is the function of helices & sheets?
Compaction of polypeptide chain = keeps proteins soluble in dense cytoplasm
Reduce the cost of burying polar backbone groups = pair polar groups efficiently
How does burying a peptide bond work? ***
What is the function of β-turn(reverse turn) structure?
Usually connects anti-parallel b-strands
Allows peptide chain to reverse direction
What is the difference between type I and type II β-turn?
Different dihedral angles
Describe the bonding in beta-turn (reverse turn) structure
Carbonyl O (i ) is H bonded to
Amide H of residue i + 3
What amino acids are most commonly found in reverse-turns?
Proline because of cyclic structure
Glycine because most sterically flexible
Both accommodate a kink
