title: A hierarchy of timescales in protein dynamics is linked to enzyme catalysis.
abstract: The synergy between structure and dynamics is essential to the function of biological macromolecules. Thermally driven dynamics on different timescales have been experimentally observed or simulated, and a direct link between micro- to milli-second domain motions and enzymatic function has been established. However, very little is understood about the connection of these functionally relevant, collective movements with local atomic fluctuations, which are much faster. Here we show that pico- to nano-second timescale atomic fluctuations in hinge regions of adenylate kinase facilitate the large-scale, slower lid motions that produce a catalytically competent state. The fast, local mobilities differ between a mesophilic and hyperthermophilic adenylate kinase, but are strikingly similar at temperatures at which enzymatic activity and free energy of folding are matched. The connection between different timescales and the corresponding amplitudes of motions in adenylate kinase and their linkage to catalytic function is likely to be a general characteristic of protein energy landscapes.
authors.affiliation: Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Henzler-Wildman
authors.forename: Ming
authors.initials: M
authors.lastname: Lei
authors.forename: Vu
authors.initials: V
authors.lastname: Thai
authors.forename: S Jordan
authors.initials: SJ
authors.lastname: Kerns
authors.forename: Martin
authors.initials: M
authors.lastname: Karplus
authors.forename: Dorothee
authors.initials: D
authors.lastname: Kern
mesh_terms: D000263:Adenylate Kinase / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry; D002384:Catalysis; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D008958:Models, Molecular; D009068:Movement; D013696:Temperature
chemical_list: D001426:Bacterial Proteins; D004798:Enzymes; D000263:Adenylate Kinase