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Step 5:
The amino acids in their natural habitat
©CMBI 2001
Hydrogen Bonds
Two electronegative atoms compete for the same hydrogen atom
Hydrogen Bond Donors (D):
Nitrogen e.g. N-H amide in peptide bond
Oxygen e.g. O-H sidechain of Ser
Hydrogen Bond Acceptors (A):
Oxygen
e.g. C=O carbonyl in peptide
bond
©CMBI 2002
Hydrogen Bonds (2)
Geometry of Hydrogen Bond D-H …. A:
Distance
H-A  2.5 Å
D-A  3.5 Å
Example: R2 N-H --- O=CR2, D-A distance = 2.9 Å
Angle
The ideal hydrogen bond would have an angle of 180° between the
lone-pair of the acceptor atom, the polar hydrogen and the donor
atom
©CMBI 2002
The -helix
• hydrogen bond between backbone carbonyl O(i) and hydrogen of N(i+4)
• 3.6 residues per turn
• right-handed helix
• a macro-dipole with positive N-terminal
©CMBI 2002
The -helix
©CMBI 2002
Helix
©CMBI 2002
Helix dipole
All peptide units point in the same direction (roughly parallel to the
helix axis)
Each peptide bond is a small dipole
The dipoles within the helix are aligned, i.e. all C=O groups point in
the same direction and all N-H groups point the other way
The helix becomes a net dipole with +0.5 charge units at the Nterminal and –0.5 at the C-terminal
By convention the dipole points from negative to positive
©CMBI 2002
Helix dipole
©CMBI 2002
-strands and -sheets
Backbone adopts an “extended” conformation
Hydrogen bonding between main chain C=O and N-H groups of two or
more adjacent -strands forms a  -sheet
Adjacent strands can be parallel or anti-parallel
R-groups extend perpendicular to the plane of the H-bonds.
R-groups of neighbouring residues within one -strand point in opposite
directions
R-groups of neighbouring residues on adjacent -strands point in the same
direction
The strand is twisted
©CMBI 2002
Antiparallel -sheet
N -> C
C <- N
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Parallel -sheet
N -> C
N -> C
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Mixed -sheet
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 Bulge
An irregularity in antiparallel  structures
Hydrogen-bonding of two residues from one strand with one
residue from the other in antiparallel  sheets
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Turns
Specialized secondary structures that allow for chain reversal
without violating conformational probabilities
Nearly one-third of the amino acids in globular proteins are found in
turns.
Most turns occur at the surface of the molecule.
©CMBI 2002
 Turns
A specific subclass is the -turn, a region of the polypeptide of 4
amino acids (i, i+1, i+2, i+3) having a hydrogen bond from O(i) to
N(i+3).
-turns can be classified into several subclasses based on the 
and  angles of residues i+1 and i+2.
Most common turn types: Type I and Type II.
©CMBI 2002
-Turns, Type I & I’
©CMBI 2002
-Hairpin
•Widespread in globular proteins.
•One of the simplest super-secondary structures
©CMBI 2002
Classes of Protein Structures
All  Topologies
All  Topologies
/ Topologies
+ Topologies
Categorized and clustered in:
CATH
SCOP
FSSP
©CMBI 2002
-Topologies
The four-helix bundle
Myohemerythrin
©CMBI 2002
 -Topologies
 sandwiches and  barrels
Immunoglobulin fold forms a  sandwich
Plastocyanin contains  barrel
©CMBI 2002
/ Topologies
/ - mixture of  and 
 unit present in
nucleotide binding proteins is
named the Rossmann Fold
Example: Flavodoxin
/ Barrel
Example: TIM triose phosphate isomerase, “TIM-barrel”
©CMBI 2002
+ Topologies
+ - both  and , but located in different domains
Examples:
Ribonuclease H
Carbonic Anhydrase
Serine protease inhibitor
©CMBI 2002
Quarternary Structure
Units of tertiary structure aggregate to form homo- or
hetero- multimers.
The individual chains are called subunits or monomers.
The subunits (polypeptide chains) may be identical (e.g.
TIM dimer) or non-identical (e.g. haemoglobin is a
tetramer and contains 2  + 2  subunits).
©CMBI 2002
Levels of Protein Structure
©George Helmkamp, Jr.