Lectures 3-5 Amino acids and motifs

Glycine
H

•All amino acids except glycine are chiral. Out of the

two chiral forms for all amino acids (L- or D- form),
only L- forms are recognized by protein synthesizing
machinary.
•Due to its small size, it can be placed in a different
category. Can occupy a wide area in the
Ramachandran plot.
•Allows for bending of the polypeptide chain.
•Largely conserved in protein sequences.
 Multiple Sequence Alignment
of Laccases
Importance of Glycine-G

1
2
3
4
5
6
7
8
9
10
11

1. Hypsizygus marmoreus 2, Coprinus comatus 3. Laccari amethyetina

4. Pholiota microspora 5. Lcc 1 with mutations 6. Laccaria bicolor 7. Leucoagaricus
8. Hypholoma sublateritium 9. Coprinopsis cinerea 10. Leucoagaricus gongylophorus
11. Pleurotus osteatus
SM Lab I-205
 Hydrophobic Amino Acids

• Contribute to hydrophobic collapse of the protein.

•Act as spacers in the interior of the protein molecules.

•Pro mis-fit in α-helix except in first few N-terminal positions. Continuity of the helix is broken
when P is there. Slows down the process of protein folding. Cis-trans isomerases are an imp part
in the folding process.
 Polar Amino acids
•Ser/Thr/Tyr/Trp H bond
with suitable donors and
acceptors or main chain –
NH/-CO
•Ser and Tyr can also be
phospho/dephosphorylated
•His can change
ionization state
depending on pH
•Forms co-ordination
complex with Fe/other
metal ions
•Found at the catalytic
site of many enzymes
Ser/Thr: O-linked glycosylation
Asn:N-linked glycosylation
•Gln/Asn can H
bond and
contribute to •Cys has a reactive SH
internal but does not ionize at
coherence and physiological pH
solubility of
proteins •Disulfide bridge
•Bind Zn, Cu,Fe atoms
 Charged Amino acids

•Asp/Glu remain as COO- •Lys/Arg are ionized at

under physiological physiological pH
conditions
•Along with Asp/Glu contribute to
•Act as protein charge of the protein molecules.
donors/acceptors in acid
base type of catalysis
•Can contribute to H bonding
 Disulfide Bridges

Cys forms disulfide bridges:

2-CH2SH + ½O2 = -CH2-S-S-CH2 + H2O

(i) This reaction, as seen, requires oxidative environment. Hence

most intracellular proteins do not make use of cysteine bridges
to fold or to make proteins stable.
(ii) These are, in general, not found in intracellular proteins. If at all,
only small proteins use this to stabilize their tertiary structure.
(iii) Their formation usually occurs in the lumen of the ER
(iv) For lending thermostability to proteins, disulfide bridges have
been introduced in several enzymes.
 Energetic stability of side chains
• Any side chain longer than that of alanine can have several different
conformations due to rotation around the bonds between the side chain carbons.
• Only those, that allow for staggered conformations, will be favored.

• Analysis of accurately determined protein structures shows that most side chains
have one or a few which occur more frequently. These are called as rotamers.
• Such rotamer libraries can be used during de novo protein modeling or for fine
tuning of the structure.
Levels of Organization-structural and functional
Peptide units, their properties
Ramachandran plot and its significance
Secondary structures-helix, strands, pleated sheet structures,
turns
Motifs
 Levels of Organization
Functional Structural
 Peptide units
Remember that peptide bond
is planar, i.e., C,O,N,H lie in
the same plane.
As a consequence, peptide
chains move along N-C or C-
C bonds.
•Peptide Units
•In a polypeptide the main chain N-Cα
and Cα-C bonds are relatively free to
rotate. These rotations are represented
by the torsion angles phi and psi,
respectively.
•Phi/Psi angles-every aa in the protein
can be defined by its unique value of
these angles.
•Φ (phi) angle: between N-Cα
•Ψ (psi) angle: between Cα-C
Ramachandran plot
 Position of Gly

+180

psi 0

-180
-180 0 phi +180
 Secondary Structures and Motifs
• Extended peptide chains are not energetically stable.
• Interior of proteins is hydrophobic and densely packed.
• Main chain C=O and N-H are to be hidden. Formation of a system of
H bonds ensures that these hydrophilic groups are hidden in the
interior of the protein.
• This hydrophobic interior is achieved through formation of α–helix
and β-sheet (made from individual β-strands) structures. Well
defined turns.
• Secondary structures provide a rigid and stable framework to which
functional groups are attached.
Alpha Helix
Consecutive amino acids
with defined phi (-600) and
psi (-500) angles.
3.6 residues per turn.
n and n + 4 H-bonding
Ends are polar
Variations such as π helix
(n, n + 5) and 310 (n , n + 3).
These occur rarely.
Alpha helices vary in
globular proteins from 4-5 to
over 40 amino acids.
 Helix formers and breakers
• Different side chains have weak but definite preferences either for
or against being in alpha helices.
• A, E, L, M are good helix formers
• P, G, Y and S are very poor.
• Such preferences were a key to early attempts to predict secondary
structures from amino acid sequences.
• The most common location for an alpha helix is along the outside of
a protein with one side facing the outside and the other facing
inwards.
• Proteins made from only alpha helices give a characteristic CD spectrum.
 Amino acid sequences of three α helices

Citrate syn
Leu – Ser – Phe – Ala – Ala – Ala - Met – Asn – Gly- Leu – Ala -

Alcohol DH Ile – Asn – Glu – Gly - Phe – Asp – Leu – Leu – Arg- Ser – Gly -

Troponin C
Lys – Glu – Asp – Ala – Lys – Gly – Lys – Ser- Glu – Glu – Glu -

260 L S F A A A MN G L A 270 K E D A G S E E
355 L N E G F OL L R S G
1 2 3 4 5 6 7 8 9 1011 365 5 6 7 8 10
1 2 3 4 5 6 7 8 9 1011
Helical wheel and its significance

• Allows to position the

alpha helix in the
protein molecule
• Leads to fairly
accurate prediction of
a structural fold and a
class.