skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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:
; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
959506
Report Number(s):
BNL-82492-2009-JA
TRN: US201016%%650
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature; Journal Volume: 450
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; AMPLITUDES; CATALYSIS; ENZYMES; FLUCTUATIONS; FREE ENERGY; PHOSPHOTRANSFERASES; PROTEINS; national synchrotron light source

Citation Formats

Henzler-Wildman,K., Lei, M., Thai, V., Jordan Kerns, S., Karplus, M., and Kern, D. A Hierarchy of Timescales in Protein Dynamics is Linked to Enzyme Catalysis. United States: N. p., 2007. Web. doi:10.1038/nature06407.
Henzler-Wildman,K., Lei, M., Thai, V., Jordan Kerns, S., Karplus, M., & Kern, D. A Hierarchy of Timescales in Protein Dynamics is Linked to Enzyme Catalysis. United States. doi:10.1038/nature06407.
Henzler-Wildman,K., Lei, M., Thai, V., Jordan Kerns, S., Karplus, M., and Kern, D. Mon . "A Hierarchy of Timescales in Protein Dynamics is Linked to Enzyme Catalysis". United States. doi:10.1038/nature06407.
@article{osti_959506,
title = {A Hierarchy of Timescales in Protein Dynamics is Linked to Enzyme Catalysis},
author = {Henzler-Wildman,K. and Lei, M. and Thai, V. and Jordan Kerns, S. and Karplus, M. and Kern, D.},
abstractNote = {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.},
doi = {10.1038/nature06407},
journal = {Nature},
number = ,
volume = 450,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}