Protein-protein interfaces: analysis of amino acid conservation in homodimers.
Evolutionary information derived from the large number of available protein sequences and structures could powerfully guide both analysis and prediction of protein-protein interfaces. To test the relevance of this information, we assess the conservation of residues at protein-protein interfaces compared with other residues on the protein surface. Six homodimer families are analyzed: alkaline phosphatase, enolase, glutathione S-transferase, copper-zinc superoxide dismutase, Streptomyces subtilisin inhibitor, and triose phosphate isomerase. For each family, random simulation is used to calculate the probability (P value) that the level of conservation observed at the interface occurred by chance. The results show that interface conservation is higher than expected by chance and usually statistically significant at the 5% level or better. The effect on the P values of using different definitions of the interface and of excluding active site residues is discussed.
Valdar
W S
WS
Biomolecular Structure and Modelling Unit, Department of Biochemistry and Molecular Biology, University College London, London, United Kingdom. valdar@biochem.ucl.ac.uk
Thornton
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D017124:Conserved Sequence; D019281:Dimerization; D019143:Evolution, Molecular; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D005810:Multigene Family; D011336:Probability; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D011506:Proteins / Q000737:chemistry*; D013499:Surface Properties
D008024:Ligands; D021122:Protein Subunits; D011506:Proteins