title: Evolutionary aspects of enzyme dynamics.
abstract: The role of evolutionary pressure on the chemical step catalyzed by enzymes is somewhat enigmatic, in part because chemistry is not rate-limiting for many optimized systems. Herein, we present studies that examine various aspects of the evolutionary relationship between protein dynamics and the chemical step in two paradigmatic enzyme families, dihydrofolate reductases and alcohol dehydrogenases. Molecular details of both convergent and divergent evolution are beginning to emerge. The findings suggest that protein dynamics across an entire enzyme can play a role in adaptation to differing physiological conditions. The growing tool kit of kinetics, kinetic isotope effects, molecular biology, biophysics, and bioinformatics provides means to link evolutionary changes in structure-dynamics function to the vibrational and conformational states of each protein.
authors.affiliation: Department of Chemistry, Department of Molecular and Cell Biology, and the California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, California 94720 and. Electronic address: klinman@berkeley.edu.
authors.forename: Judith P
authors.initials: JP
authors.lastname: Klinman
authors.affiliation: Department of Chemistry, The University of Iowa, Iowa City, Iowa 52242-1294. Electronic address: amnon-kohen@uiowa.edu.
authors.forename: Amnon
authors.initials: A
authors.lastname: Kohen
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000235:genetics; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D055162:Biocatalysis; D020134:Catalytic Domain; D019143:Evolution, Molecular; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D000426:Alcohol Dehydrogenase; D013762:Tetrahydrofolate Dehydrogenase
keywords: Alcohol Dehydrogenase (ADH); Enzyme; Enzyme Catalysis; Enzyme Kinetics; Enzyme Mechanism; Enzyme Mutation; Evolution; Folate Metabolism; Molecular Evolution; Protein Evolution