title: Linkage between dynamics and catalysis in a thermophilic-mesophilic enzyme pair.
abstract: A fundamental question is how enzymes can accelerate chemical reactions. Catalysis is not only defined by actual chemical steps, but also by enzyme structure and dynamics. To investigate the role of protein dynamics in enzymatic turnover, we measured residue-specific protein dynamics in hyperthermophilic and mesophilic homologs of adenylate kinase during catalysis. A dynamic process, the opening of the nucleotide-binding lids, was found to be rate-limiting for both enzymes as measured by NMR relaxation. Moreover, we found that the reduced catalytic activity of the hyperthermophilic enzyme at ambient temperatures is caused solely by a slower lid-opening rate. This comparative and quantitative study of activity, structure and dynamics revealed a close link between protein dynamics and catalytic turnover.
authors.affiliation: Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Magnus
authors.initials: M
authors.lastname: Wolf-Watz
authors.forename: Vu
authors.initials: V
authors.lastname: Thai
authors.forename: Katherine
authors.initials: K
authors.lastname: Henzler-Wildman
authors.forename: Georgia
authors.initials: G
authors.lastname: Hadjipavlou
authors.forename: Elan Z
authors.initials: EZ
authors.lastname: Eisenmesser
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kern
mesh_terms: D000263:Adenylate Kinase / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D000263:Adenylate Kinase