title: Emergence of diverse biochemical activities in evolutionarily conserved structural scaffolds of proteins.
abstract: Comparative analysis of numerous protein structures that have become available in the past few years, combined with genome comparison, has yielded new insights into the evolution of enzymes and their functions. In addition to the well-known diversification of substrate specificities, enzymes with several widespread catalytic folds, particularly the TIM barrel, the RRM-like domain and the double-stranded beta-helix (cupin) domain, have been extensively explored in 'reaction space', resulting in the evolution of numerous, diverse catalytic activities supported by the same structural scaffold. Common protein folds differ widely in the diversity of catalyzed reactions. The biochemical plasticity of a fold seems to hinge on the presence of a generic, symmetrical substrate-binding pocket as opposed to highly specialized binding sites.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Anantharaman
authors.forename: L
authors.initials: L
authors.lastname: Aravind
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
mesh_terms: D002384:Catalysis; D017124:Conserved Sequence; D004798:Enzymes / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D019143:Evolution, Molecular; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D040681:Structural Homology, Protein
chemical_list: D004798:Enzymes; D011506:Proteins