A hierarchy of timescales in protein dynamics is linked to enzyme catalysis.
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.
Henzler-Wildman
Katherine A
KA
Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA.
Lei
Ming
M
Thai
Vu
V
Kerns
S Jordan
SJ
Karplus
Martin
M
Kern
Dorothee
D
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
D001426:Bacterial Proteins; D004798:Enzymes; D000263:Adenylate Kinase