期刊
SCIENCE
卷 355, 期 6322, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aag2355
关键词
-
资金
- Canadian Institutes of Health Research Training Program in Protein Folding and Interaction Dynamics
- Ontario Graduate Scholarship
- Ontario Student Opportunity Trust
- CREST/JST
- Natural Sciences and Engineering Research Council of Canada [418679, RGPIN-2015-04877]
- Canadian Institutes of Health [MOP-130461]
- Canada Research Chairs Program
- Canada Foundation for Innovation under Compute Canada
- Government of Ontario
- Ontario Research Fund-Research Excellence
- University of Toronto
Freeze-trapping x-ray crystallography, nuclear magnetic resonance, and computational techniques reveal the distribution of states and their interconversion rates along the reaction pathway of a bacterial homodimeric enzyme, fluoroacetate dehalogenase (FAcD). The crystal structure of apo-FAcD exhibits asymmetry around the dimer interface and cap domain, priming one protomer for substrate binding. This asymmetry is dynamically averaged through conformational exchange on a millisecond time scale. During catalysis, the protomer conformational exchange rate becomes enhanced, the empty protomer exhibits increased local disorder, and water egresses. Computational studies identify allosteric pathways between protomers. Water release and enhanced dynamics associated with catalysis compensate for entropic losses from substrate binding while facilitating sampling of the transition state. The studies provide insights into how substrate-coupled allosteric modulation of structure and dynamics facilitates catalysis in a homodimeric enzyme.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据