©CMBI 2001 Step 5: The amino acids in their natural habitat

©CMBI 2002 Hydrogen Bonds Two electronegative atoms compete for the same hydrogen atom Hydrogen Bond Donors (D): Nitrogene.g. N-H amide in peptide bond Oxygene.g. O-H sidechain of Ser Hydrogen Bond Acceptors (A): Oxygene.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 N- terminal 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

©CMBI 2002 Parallel  -sheet N -> C

©CMBI 2002 Mixed  -sheet

©CMBI 2002  Bulge An irregularity in antiparallel  structures Hydrogen-bonding of two residues from one strand with one residue from the other in antiparallel  sheets

©CMBI 2002 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).

Levels of Protein Structure ©George Helmkamp, Jr.