Dawn Of The Proteins Flashcards
Why did proteins evolve?
- better catalysts
- more chemistry
- smaller units
- hydrophobic core
Describe the small amino acids
Both hydrophilic and hydrophobic
List the small amino acids
- Glycine
- Proline
Describe glycine
Gly, G
Flexible
Describe proline
Pro, P
Inflexible, bends chain
List the non-polar/hydrophobic amino acids
- Alanine
- Isoleucine
- Leucine
- Methionine
- Phenylalanine
- Tryptophane
- Tyrosine
- Valine
Which of the non-polar/hydrophobic amino acids are aliphatic
- Alanine
- Isoleucine
- Leucine
- Methionine
- Valine
Which of the non-polar/hydrophobic amino acids are aromatic
- Phenylalanine
- Tryptophane
- Tyrosine
What is the hydrophobic effect?
Non-polar side chains tend to pack together
List the polar, uncharged amino acids
- Asparagine
- Cysteine
- Glutamine
- Serine
- Threonine
Describe cysteine
Cys, C
Makes disulphide bridges (S-S bonds)
Describe polar/uncharged amino acids
Solvent exposed, hydrogen bridges, can be post-translationally modified
List the charged amino acids
- Arginine
- Aspartate
- Glutamate
- Histidine
- Lysine
Describe the basic amino acids in principal
They have a positive charge, N has an extra proton (H+)
Describe the acidic amino acids in principal
Negative charge, COOH has lost proton
You then use -ate suffix
Alanine
Ala, A
Valine
Val, V
Leucine
Leu, L
Isoleucine
Ile, I
Methionine
Met, M
Phenylalanine
Phe, F
Tyrosine
Tyr, Y
Tryptophane
Trp, W
Serine
Ser, S
Threonine
Thr, T
Asparagine
Asn, N
Glutamine
Gln, Q
Lysine
Lys, K
pKa = 10.53
Arginine
Arg, R
pKa = 12.48
Histidine
His, H
pKa = 6.0
Aspartate
Asp, D
pKa = 3.86
Glutamate
Glu, E
pKa = 4.25
List the charged amino acids
- Arginine
- Aspartate
- Glutamate
- Histidine
- Lysine
Describe charged amino acids
Solvent exposed, charged at neutral pH, can co-ordinate metals/ions
How many AA are there?
20
Of which amino acids were there sufficient to be prebiotic
A, D, E, G, I, L, P, S, T, V
What is the prebiotic amino acid hypothesis
Proteins may have evolved with <10aa; additional aas evolved later
What are the qualities of an amino acid that you need to learn?
- Aromatic/aliphatic
- Basic/acidic
- Polar/non-polar
- It’s name :)
A peptide bond is
- Fixed in plane (cannot rotate)
- a partial double bond (resonance structure)
How many aas does a peptide have?
<50
How many aas does a protein have?
> 50aa
Peptide/protein backbone nomenclature
NH-Cα-CO
Peptide/protein side chains nomenclature
R
Directionality of a peptide/protein
N-terminus (amino) -> C-terminus (carboxy)
What is the primary protein structure
Sequence of a chain of amino acids
What is the secondary protein structure
Local folding of the polypeptide chain into helices or sheets
What is tertiary protein structure?
3D folding pattern (shape) of a protein due to side chain interactions (mediated by residue side chains)
Quaternary protein structure
Protein consisting of more than one aa chain
Describe the formation of the secondary structure of proteins/peptides
- backbone has a H-bond donor (N-H) and acceptor (C=O)
- backbones folds itself in two main ways: α-helix and β-sheet
- easy interactions through H-bonds
Describe an α-helix
- 3.6 residues per turn
- side chains exposed outwards
Describe β-sheets
- can be parallel or anti-parallel
- side chains exposed outwards
Describe the types of tertiary structure
- Hydrophobic effect
- Disulphide bridges
- H-bonds between polar aa
- Ionic bonds between charged aa
What type of protein helps with folding?
Chaperones
Proteins naturally seek the
Lowest energy state
List some things that cause dénaturation
- Acids
- Bases
- Detergents
- Heat
- Salt
- Solvent
What does dénaturation cause?
Protein to go from folded to unfolded
List the two forms of conformational change
- Induced fit
- Allosteric regulation
Describe allosteric regulation
- binding of a molecule at a site other than the active site
What is allosteric regulation more generally described as
Enzyme regulation
Give an example of induced fit
Fructose binding to rhamnulose kinase
Give an example of allosteric regulation
- Binding of O2 to one subunit in homotetramer of hémoglobin promotes O2 binding to other subunits
- Co-operatic it’s via conformational change
Give an example of conformational change
Human α-macroglobin traps proteases
Give examples of metal ions as cofactors
- Zn2+ in zinc finger protein
- Zn2+ in carboxypeptidase
- Ca2+ in calmodulin
- 2Fe-2S cluster in redox protein
Give an example of a non-metal ion based cofactor
NADPH cofactor bound to aldehyde dehydrogenase
Define post-translational modifications (PTMs)
- Covalent modification of proteins
- often reversible and enzymatic
- regulate proteins by altering surface proteins
Give examples of PTMs
- Acetylation
- Acylation/lipidation
- Glycosylation
- Hydroxylation
- Methylation
- Nitrosylation
- Phosphorylation
Phosphorylation
Addition of a phosphate group
Nitrosylation
Addition of N=O onto cysteine residues
Acylation/lipidation
Addition of lipid onto cysteine residue
Hydroxylation
Addition of a H onto an O
Glycosylation
Addition of a glucose onto -NH
Acetylation
Addition of an acetyl group onto -NH
Methylation
Addition of methyl groups onto -NH
Describe the chemistry of RNA
- 4 bases
- ~340Da
- no hydrophobic core
Describe the chemistry of proteins
- 20 various bases
- ~110Da
- yes hydrophobic core
Describe proteins relative to RNA
‘Smaller molecular machines with more chemistry; better for catalysis’
Does protein self-replicate
- no
- interactions in antiparallel β-sheets (that might look like DNA) are between backbones, not residues
How are cyclic peptides made?
- non-ribosomal peptide synthétases (NRPS)
- polyketide synthases (PKS)
Give an example of a cyclic peptide
Antibiotics
Describe cyclic peptides
- unusual aas
- D-enantiomers
- cyclisation
What happens to amino acids in water?
Proton donation from carboxyl to amine group
Why does steric hindrance arise?
From side chains
Where is proline found?
- in loops and bends
- small; little steric hindrance
What is interesting about the smallness of glycine and proline?
Can be found in hydrophilic and hydrophobic environments
Why is Tryptophane apolar?
Benzyl group
Why is tyrosine polar?
Hydroxyl group gives polarity
Where does the hydrophobic effect occur?
In the core of the protein
What does the hydrophobic effect entail?
Protein cannot interact with water
Why are disulphide bridges good?
They are strong; stabilise proteins
Why are polar, uncharged amino acids generally involved in interactions with water?
Due to polarisation and hydrogen bonds
What is the special capability of N?
It can carry an extra proton
What happens if you go above pKa?
- Protons are taken
- residues become uncharged
Papain =
An enzyme
Define backbone
Coupled amino acids without side chains
Define residues
Amino acids when bonded, because there are no longer amino or acid groups
Folding reduces
Steric hindrance
Cofactors help in:
- Catalysis
- Structure
Hydrogen bonds do what to a molecule?
Stabilise it
Methylation does what?
Reduces positive charge of lysine
What does the hydrophobic core allow?
Embedding in membranes
Why is peptide size restricted initially?
Lack of translation machinery
