title: Enzyme promiscuity: engine of evolutionary innovation.
abstract: Catalytic promiscuity and substrate ambiguity are keys to evolvability, which in turn is pivotal to the successful acquisition of novel biological functions. Action on multiple substrates (substrate ambiguity) can be harnessed for performance of functions in the cell that supersede catalysis of a single metabolite. These functions include proofreading, scavenging of nutrients, removal of antimetabolites, balancing of metabolite pools, and establishing system redundancy. In this review, we present examples of enzymes that perform these cellular roles by leveraging substrate ambiguity and then present the structural features that support both specificity and ambiguity. We focus on the phosphatases of the haloalkanoate dehalogenase superfamily and the thioesterases of the hotdog fold superfamily.
authors.affiliation: Bioinformatics Graduate Program and Boston University, Boston, Massachusetts 02215.
authors.forename: Chetanya
authors.initials: C
authors.lastname: Pandya
authors.affiliation: Department of Chemistry, Boston University, Boston, Massachusetts 02215 and.
authors.forename: Jeremiah D
authors.initials: JD
authors.lastname: Farelli
authors.affiliation: Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131. Electronic address: dd39@unm.edu.
authors.forename: Debra
authors.initials: D
authors.lastname: Dunaway-Mariano
authors.affiliation: Bioinformatics Graduate Program and Boston University, Boston, Massachusetts 02215; Department of Chemistry, Boston University, Boston, Massachusetts 02215 and. Electronic address: drkallen@bu.edu.
authors.forename: Karen N
authors.initials: KN
authors.lastname: Allen
mesh_terms: D000818:Animals; D055162:Biocatalysis; D020134:Catalytic Domain; D004798:Enzymes / Q000737:chemistry* / Q000235:genetics; D019143:Evolution, Molecular; D006801:Humans; D008958:Models, Molecular; D013379:Substrate Specificity
chemical_list: D004798:Enzymes
keywords: Enzyme Catalysis; Hydrolase; Phosphatase; Protein Evolution; Structural Biology