title: Topological variation in the evolution of new reactions in functionally diverse enzyme superfamilies.
abstract: In functionally diverse enzyme superfamilies (SFs), conserved structural and active site features reflect catalytic capabilities 'hard-wired' in each SF architecture. Overlaid on this foundation, evolutionary changes in active site machinery, structural topology and other aspects of structural organization and interactions support the emergence of new reactions, mechanisms, and substrate specificity. This review connects topological with functional variation in each of the haloalkanoic acid dehalogenase (HAD) and vicinal oxygen chelate fold (VOC) SFs and a set of redox-active thioredoxin (Trx)-fold SFs to illustrate a few of the varied themes nature has used to evolve new functions from a limited set of structural scaffolds.
authors: Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, CA 94158-2517, USA.
authors: Elaine C
authors: EC
authors: Meng
authors: Patricia C
authors: PC
authors: Babbitt
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D017124:Conserved Sequence; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D006867:Hydrolases / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D013379:Substrate Specificity; D013879:Thioredoxins / Q000737:chemistry
chemical_list: D004798:Enzymes; D013879:Thioredoxins; D006867:Hydrolases; C034507:2-haloacid dehalogenase