Substrate recognition drives the evolution of serine proteases.
A method is introduced to identify amino acid residues that dictate the functional diversity acquired during evolution in a protein family. Using over 80 enzymes of the chymotrypsin family, we demonstrate that the general organization of the phylogenetic tree and its functional branch points are fully accounted for by a limited number of residues that cluster around the active site of the protein and define the contact region with the P1-P4 residues of substrate.
Rose
Thierry
T
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Di Cera
Enrico
E
D000465:Algorithms; D000818:Animals; D002918:Chymotrypsin / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D015233:Models, Statistical; D005810:Multigene Family; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000235:genetics*; D012984:Software; D013379:Substrate Specificity
D012697:Serine Endopeptidases; D002918:Chymotrypsin