Topic 2

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An overview of amino acid structure
Topic 2
Biomacromolecule
• A naturally occurring substance of large molecular weight e.g. Protein,
DNA, lipids etc.
• Proteins form the class of bio-macromolecule that have the most welldefined physicochemical properties and were generally easier to isolate and
characterize than nucleic acids, polysaccharides or lipids.
• Proteins are essential to biochemical functions.
• The monomeric unit of protein is called the amino acids
Amino Acids
 Proteins are linear polymers of amino acids connected by peptide bonds –
amino acids are the building blocks of proteins
There are 20 standard amino acids. Asparagine was first found in 1806 and the
last amino acid discovered (Threonine) was in 1938 (over 130 years later!!)
All 20 amino acids share common structural features: -amino acids
--each has a carboxyl group and an amino group bonded to the same -carbon
--differ in R group or side chain
R Side-chain
H3N+
Ca
COOCarboxyl
Group
Amino group
H
spacefill
Ball and stick
Amino Acids
Amino Acid ionization
Amino Acid ionization
Amino Acids
Lehninger Principles of Biochemistry
Amino Acids
3-Letter
1-Letter
Alanine
Arginine
Asparagine
Aspartic acid
Cysteine
Glutamic acid
Glutamine
Glycine
Histidine
Isoleucine
Leucine
Lysine
Methionine
Phenylalanine
Proline
Serine
Threonine
Tryptophan
Tyrosine
Valine
Ala
Arg
Asn
Asp
Cys
Glu
Gln
Gly
His
Ile
Leu
Lys
Met
Phe
Pro
Ser
Thr
Trp
Tyr
Val
A
R
N
D
C
E
Q
G
H
I
L
K
M
F
P
S
T
W
Y
V
Grouping of Amino Acids
Some important terms:
 Hydrophobic: tending to avoid an aqueous environment. Hydrophobic
molecules are non-polar and uncharged. Amino acids with this property are
usually buried within the hydrophobic core of the protein.
Aliphatic: carbon atoms are joined together in straight or branched open
chains rather than in rings.
Aromatic: contains an aromatic ring system.
 Hydrophilic: tending to interact with water. Hydrophilic molecules are polar
and charged. Generally found on protein surface and exposed to aqueous
environment.
 Amphipathic: having both polar and nonpolar character.
Classification of amino acids is “fuzzy”. There are several different grouping schemes.
Our classification hierarchy
It’s actually quite a bit more complicated…
Stereoisomers of Amino Acids
web99.arc.nasa.gov/~astrochm/




A "chiral" molecule cannot be superimposed with its mirror image
The amino acid residues in proteins are almost exclusively L-stereroisomers
D-amino acids are only found in a few small molecules
Glycine does not have a chiral center
Nomenclature of Side Chain Atoms
atomic symbol remoteness indicator branch designator
C, N, O, S
Greek letters
"A" for alpha,
"B" for beta,
"G" for gamma,
"D" for delta,
"E" for epsilon,
"Z" for zeta, and
"H" for eta.
1, 2, 3…
Atom nomenclature within amino acids
(as used within the PDB)
O
N
CA
C
CB
CG2
OG1
Atom nomenclature within amino acids (as
used within the PDB)
-The alpha carbon (CA) is immediately adjacent the most oxidized carbon (which is
the CO2- in amino acids)
-All the other heavy nuclei are named according to the Greek alphabet.
-Put otherwise, LYS can be described by: CA, CB, CG, CD, CE, and NZ.
Lys
To Do: Learn how to name the atoms of all amino acids.
Hint: look at any generic PDB file to get a list of atom types.
Arg
Numbers are used to discriminate between similar positions…
CB
CB
CB
CG
CG
CD1
CG2
CD2
OG1
OD1
ND2
Here are some harder examples…
CB
CB
CG
CD2
NE2
ND1
CE1
CD1
CE2
CG
CZ
CD2
CE2
OH
CB
CG
CD1
NE1
CD2
CE3
CZ3
CH2
CE2
CZ2
Nomenclature of Side Chain Atoms
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
ATOM
2518
2519
2520
2521
2522
2523
2524
2525
2526
2527
2528
2529
2530
2531
2532
2533
2534
2535
2536
2537
2538
2539
2540
2541
2542
2543
2544
2545
2546
2547
2548
2549
CB
CG
CD
NE
CZ
NH1
NH2
N
CA
C
O
CB
CG
CD1
CD2
CE1
CE2
CZ
OH
N
CA
C
O
CB
CG
CD1
CD2
CE1
CE2
CZ
N
CA
ARG
ARG
ARG
ARG
ARG
ARG
ARG
TYR
TYR
TYR
TYR
TYR
TYR
TYR
TYR
TYR
TYR
TYR
TYR
PHE
PHE
PHE
PHE
PHE
PHE
PHE
PHE
PHE
PHE
PHE
ASP
ASP
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
100
100
100
100
100
100
100
100A
100A
100A
100A
100A
100A
100A
100A
100A
100A
100A
100A
100B
100B
100B
100B
100B
100B
100B
100B
100B
100B
100B
101
101
10.115
10.970
12.115
12.888
14.066
14.620
14.687
7.182
6.427
6.376
6.716
5.008
4.153
3.708
3.761
2.890
2.948
2.513
1.690
5.974
5.892
4.477
4.048
6.908
8.332
8.834
9.143
10.126
10.438
10.928
3.762
2.369
0.762
0.968
-0.023
0.203
-0.354
-1.175
-0.088
2.284
2.198
3.604
4.584
1.657
2.469
3.754
1.934
4.480
2.648
3.916
4.600
3.698
4.983
5.207
4.587
5.020
4.891
3.656
6.014
3.538
5.911
4.669
6.107
6.394
57.410
58.664
58.757
59.977
60.234
59.353
61.380
55.730
54.486
53.886
54.555
54.732
55.689
55.357
56.914
56.224
57.788
57.440
58.311
52.623
51.943
51.440
50.470
50.798
51.268
51.668
51.385
52.185
51.902
52.302
52.113
51.790
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
1.00
16.08
14.49
17.17
16.50
17.58
13.62
17.77
12.75
14.21
14.53
15.84
14.11
14.04
14.99
14.26
14.63
13.06
17.73
16.51
14.33
14.40
14.15
12.86
15.51
17.82
17.78
17.58
17.48
16.89
15.82
16.17
17.29
C
C
C
N
C
N
N
N
C
C
O
C
C
C
C
C
C
C
O
N
C
C
O
C
C
C
C
C
C
C
N
C
Side-chain torsion angles
Side Chain Torsion Angles
Number of 
No 
Amino Acid Types
Gly, Ala
Only one 1
Cys, Ser, Thr, Val
1 ,2
Asn, Asp, His, Ile, Leu, Phe, Tyr, Trp
1 ,2, 3
Gln, Glu, Met
1 ,2, 3 ,4
Lys
1 ,2, 3 ,4, 5
Arg
Take this amino acid as an example
Side Chain Torsion Angles
 It has been shown in the 70s by Janin et al. that different side-chain
conformations do not have equal distribution over the dihedral angle space.
Rather they tend to cluster at specific regions of the space.
Janin J, Wodak S. “Conformation of amino acid side-chains in proteins”, J Mol Biol.
1978,125(3):357-86
Side Chain Torsion Angles
Distribution of side-chain torsion angles for 6,638 leucine residues (403 crystal
structures). The two major rotamers are labeled "1" and "2“.
G.J. Kleywegt and T.A. Jones, Acta Cryst. D54, 1119-1131 (1998).
Right image from Dunbrack’s lab
Side-chain torsion angles
-With the exception of Ala and Gly, all sidechains
also have torsion angles.
-To Do on your own:
-
Count the # of chi’s in each amino acid.
Determine why Ala doesn’t have a chi angle.
Side Chain Rotamers
 Rotamer: Rotational isomer
 Rotamers are generally defined as low energy side-chain
conformations.
 Rotamers are knowledge-based. They are derived from
statistical analysis of sidechain conformations in known protein
structures through clustering observed conformations or by
dividing torsion angle space into bins and determining an average
conformation in each bin
Rotamer libraries: collections of rotamers for each residue type.
In general, rotamer libraries contain information about both the
conformation and the frequency of a certain conformation. There
are several different types of rotamer libraies.
Side Chain Torsion Angles
 The different conformations of the
sidechain as a function of χ1are referred to as
gauche(+), trans and gauche(-).
 The amino acid is viewed along the CβCα bond
www.cryst.bbk.ac.uk

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