Lecture 4 - building blocks of proteins Flashcards
What makes up an amino acid? Properties of these features?
Amino group - basic NH2
Side chain - R group determines the characteristics (size, polarity, and pH) for each type of amino acid.
Carboxyl group - acidic COOH
What does it mean when you say that amino acids are chiral?
The chiral carbon has four different groups attached so the compound can exist as a pair of non-superimposable mirror images. There are L or D forms
L and D form
All amino acids except for glycine are stereoisomers. This means that there are mirror images of their structure. It is just like how we have left hands and right hands. These are labeled L (left-handed) and D (right-handed) to distinguish the mirror images.
L spells out CO-R-N, L form dominates nature
Amino acids in solution as zwitterions
An amino acid has this ability because at a certain pH value (different for each amino acid) nearly all the amino acid molecules exist as zwitterions. If acid is added to a solution containing the zwitterion, the carboxylate group captures a hydrogen (H+) ion, and the amino acid becomes positively charged. If base is added, ion removal of the H+ ion from the amino group of the zwitterion produces a negatively charged amino acid. In both circumstances, the amino acid acts to maintain the pH of the system—that is, to remove the added acid (H+) or base (OH−) from solution.
Zwitterions
an overall neutral species in which two or more atoms bear opposite formal charges
How many amino acids are there?
20 of them - each have a common backbone but different side chains
Side chains
Different side chains in different amino acids
In proteins these bits are arranged to carry out chemical reactions
4 main groups of amino acids as discussed in lectures
Non polar Uncharged polar Negatively charged (acidic) polar Positively charged (basic) polar
Where in a protein would you expect to find non-polar amino acid residues?
On the inside of a protein structure
The names of the amino acids can be abbreviated in both _____ letter and _____ letter codes.
Three
Single
Non polar amino acids
C - cysteine A - Alanine M - Methionine P - Proline F - Phenylalanine I - Isoleucine G - Glycine V - Valine L - Leucine W - Tryptophan
G
Glycine Not chiral (2 same atoms) More flexible because it doesn’t have bulky groups hanging off of it - ends up being found in places with tight turns Almost in a group on its own R group = H
C
Cysteine
Can dorm disulphide bonds
Can she H+ and become negatively charged nucleophile and work in the active site of enzymes called cysteine proteases
General statement about the placement of polar and non-polar amino acids
Generally non-polar amino acids get put inside a protein and polar/charged amino acids decorate the surface because the cytoplasm is predominantly salt and water
Charged and polar therefore tend to be on the surface of proteins or if they are inside they will usually have their charge tied up in an ionic bond or they will be involved in the active site of an enzyme
F and W
F = Phenylalanine
W= Tryptophan
Both have aromatic rings in their side chains
M
Methionine
Quite bulky and hydrophobic
P
Proline
Quite rigid and therefore is important in structure because of this rigidity
Uncharged polar amino acids
S = Serine (alanine that has been hydroxylated)
T = Threonine, 3 carbons and internal one has been hydroxylated
Y = Tyrosine, looks like Phe only with hydroxyl attached
N = asparagine
Q= glutamine
negatively charged (acidic) polar amino acids
D = aspartic acid, involved in lots of active sites
E = Glutamic acid, extra methyl group to Asp
Donate protons
positively charged (basic) polar amino acids
K = Lysine which has 4 methyl groups and one amino group at end which makes up the R group
R= Arginine
H = Histidine
Take up protons
One letter abbreviations are useful for
Sequence alignment and mutations
One letter abbreviations
First letter - wild type or native amino acid (original amino acid)
Number - Location of amino acid
Second letter - mutated residue
What chemical groups would we expect to find in the R-group of an ionisable amino acid?
COOH, SH, OH, NH2/3+
Where in a protein would we often find ionisable amino acid residues?
Arranged on the surface in contact or near solvent
Which amino acids have ionisable side chains ?
Acidic amino acids - aspartic acid, glutamic acid (pka 4)
Basic amino acids - Histidine (pka 6), lysine (pka 10) and arginine (pka 12.5)
Non-polar - cysteine (pka 8), tyrosine (pka 10)
What is pka?
The pka value for an ionisable group on an amino acid or protein is the pH at which the group is 50% ionised
What is pI?
Isoelectric point is the pH at which the net charge on an amino acid (or protein) is zero
Post-translational modification
This is defined as modifications that occurs to some amino acids after they are added to a protein
List some common examples of post-translational modifications and their functions
Phosphorylation (control of enzyme activity), hydroxylation (needed to prevent connective tissue disease and scurvy),
carboxylation (needed for blood clotting)
Cysteine and cyestine forming bonds with each other
If you have 2 cysteine that are close to one another in a protein and in an oxidising environment the 2 sulphide groups can form a disulphide bond - common in extracellular proteins and not so common in intracellular proteins
Example of a post-translational modification
Amino acid modifications
Phosphorylation Hydroxylation Carboxylation Metal binding Iodination Glycosylation Many others
What can amino acid modifications do?
Can change solubility and activity
Phosphorylation
Control of enzyme activity - often on/off
Hydroxylation
Needed to prevent connective tissues diseases and scurvy
Add -OH group
Carboxylation
Needed for blood clotting
Adds carboxylate group
Peptide bond
Proteins are made up by joining amino acids together with a covalent bond that is called a peptide bond
Peptide
A short stretch of amino acids joined together by peptide bonds is called a peptide
Protein
A longer chain of amino acids joined together, usually with a defined biological function, is a protein
Amino acid residues
When amino acids bond together, they are referred to as amino acid residues as they are no longer complete, individual amino acids (removed water, what remains after the reaction)
Peptide bond defining features
40% double bond character leads to planarity
Planar conformation maximises pi bond overlap
Rotational barrier of 80 kj/mol
The peptide bond is predominantly trans - the alpha carbons are on opposite sides of the peptide bonds
Planar, trans, dipole
What chemical groups would be on an R-group of an ionizable amino acid
OH groups and NH groups
Alanine
Ala, A
Valine
Val, V
Leucine
Leu, L
Isoleucine
Ile, I
Glycine
Gly, G
Cysteine
Cys, C
Phenylalanine
Phe, F
Tryptophan
Trp, W
Methionine
Met, M
Proline
Pro, P
Serine
Ser, S
Threonine
Thr, T
Tyrosine
Tyr, Y
Asparagine
Asn, N
Glutamine
Gln, Q
Aspartic acid
Asp, D
Glutamic acid
Glu, E
Lysine
Lys, K
Arginine
Arg, R
Histidine
His, H
which amino acids are ionisable at physiological pH?
Asp, Glu, His, Lys, Arg
which amino acids are ionisable but not at physiological pH?
Cys, Tyr
rotational barrier of peptide bonds
80 kJ/mol
how much of the peptide bond is double?
40%
Another name for a peptide bond
amide bond
