Transcript No Slide Title

Amino Acids
“When you understand the amino acids,
you understand everything”
©CMBI 2001
Amino Acids
Proteins are macromolecules made up from 20 different amino acids.
The heart of the amino acid is the so-called C. To which are bound: an
amino group, a carboxyl group, a hydrogen, and the side chain.
O
H2N
C
CH

OH
R
The C, C, N and O atoms are called backbone atoms.
R denotes any one of the 20 possible side chains.
©CMBI 2001
Amino Acids
Backbones run from the amino to the carboxy end, or in other
words, from N-terminus to C-terminus.
©CMBI 2001
Zwitterion
At pH 7, the amino group and the carboxyl groups are both ionised.
In this state the amino group is
protonated and thus positive, and
the carboxyl group is de-protonated,
and thus negative.
O
+
H3N
C
An amino acid in this polarised
state is called a zwitterion.
CH
In a protein, there is only one H on
the N, and only one O on the C.
R

O
©CMBI 2001
-
Di-peptide
Amino acids bind, to form a
protein. Upon binding, two
protons from the NH3 and
one oxygen from the
carboxyl join to form a water.
So the peptide bond has at
the one side a C=O and at
the other side an N-H.
Only the ends of the chain
are NH3 or carboxylic.
Which dipeptide is this?
©CMBI 2001
The Peptide Bond
H2N
f
CH
R1

O
R2
C
CH

OH
N
C
H
O
phi ()
psi ()
= torsion angle around N-CA bond
= torsion angle around CA-C bond
omega ()
= always ~180 degrees, sometimes ~0
= bond between two amino acids; peptide bond
©CMBI 2001
Phi-Psi
©CMBI 2001
Amino Acid Sequence
The amino acid sequence (also called primary structure) of a
protein is the order of the amino acids in the protein chain.
The sequence is always read from the N-terminus to the Cterminus of the protein.
For example:
+H3N-Lys-Val-Phe-Ala-Met-Cys-Leu-Leu-Arg-Val-COO-
Or (in one-lettercode):
KVFAMCLLRV
©CMBI 2001
Direction of Protein Chain
Lys-Val
Val-Lys
©CMBI 2001
The 20 Amino Acids
A
C
D
E
F
G
H
I
K
L
M
N
P
Q
R
S
T
V
W
Y
Ala
Cys
Asp
Glu
Phe
Gly
His
Ile
Lys
Leu
Met
Asn
Pro
Gln
Arg
Ser
Thr
Val
Trp
Tyr
Alanine
Cysteine
Aspartic acid (Aspartate)
Glutamic acid (Glutamate)
Phenylalanine
Glycine
Histidine
Isoleucine
Lysine
Leucine
Methionine
Asparagine
Proline
Glutamine
Arginine
Serine
Threonine
Valine
Tryptophan
Tyrosine
©CMBI 2001
The 20 Amino Acids
©CMBI 2001
20 Amino Acids
The side chains, R, determine the differences in the structural and
chemical properties of the 20 ‘natural’ amino acids.
The 20 amino acids can, for example, be classified as follows:
Aliphatic/hydrophobic
Polar
Alcoholic
Sulfur-containing
Aromatic
Charged
Special
Ala, Leu, Ile, Val
Asn, Gln
Ser, Thr, (Tyr)
Met, Cys
Phe, Tyr, Trp, (His)
Arg, Lys, Asp, Glu, (His)
Gly (no R), Pro (cyclic, imino-acid)
Several amino acids belong in more than one category.
©CMBI 2001
Amino Acid Characteristics
There are many ways to characterize the properties of amino acids.
The ones most useful and most commonly used are:
Hydrophobicity
Size
Charge
Secondary structure preference
Alcoholicity
Aromaticity
And on top of that there are some special characteristics like bridge
forming by cysteines, rigidity of prolines, titrating at physiological
pH of histidine, flexibility of glycines, etc.
©CMBI 2001
Hydrophobicity
Hydrophobicity is the most important characteristic of amino acids.
It is the hydrophobic effect that drives proteins towards folding.
Actually, it is all done by water. Water does not like hydrophobic
surfaces. When a protein folds, exposed hydrophobic side chains
get buried, and release water of its sad duty to sit against the
hydrophobic surfaces of these side chains.
Water is very happy in bulk water because there it has on average
3.6 H-bonds and about six degrees of freedom.
So, whenever we discuss protein structure, folding, and stability, it
is all the entropy of water, and that is called the hydrophobic effect.
©CMBI 2001
Secondary Structure Preference
Amino acids form chains, the sequence or primary structure.
These chains fold in -helices, b-strands, b-turns, and loops (or for
short, helix, strand, turn and loop), the secondary structure.
These secondary structure elements fold further to make whole
proteins, but more about that later.
There are relations between the physico-chemical characteristics of
the amino acids and their secondary structure preference. I.e., the
b- branched residues (Ile, Thr, Val) like to sit in b-strands.
©CMBI 2001