西亚试剂：Intrinsic motions along an enzymatic reaction trajectory

发布时间：2025-09-13

Intrinsic motions along an enzymatic reaction trajectory

Katherine A. Henzler-Wildman1, Vu Thai1, Ming Lei1, Maria Ott3, Magnus Wolf-Watz1,6, Tim Fenn2,6, Ed Pozharski2,6, Mark A. Wilson2,6, Gregory A. Petsko2, Martin Karplus4,5, Christian G. Hübner3,6 & Dorothee Kern1

Department of Biochemistry and Howard Hughes Medical Institute,
Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454, USA
Institute of Physics, Martin Luther-University Halle-Wittenberg, D-06120 Halle, Germany
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA
Laboratoire de Chimie Biophysique, ISIS, Université Louis Pasteur, F-67000 Strasbourg, France
Present addresses: University of Umeå, Department of Chemistry, SE-90187 Umeå, Sweden (M.W.-W.); Departments of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA (T.F.); Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland 21201, USA (E.P.); Department of Biochemistry and the Redox Biology Center, University of Nebraska, Lincoln, Nebraska 68588, USA (M.A.W.); University at Lübeck, Institute of Physics, 23538 Lübeck, Germany (C.G.H.).

Correspondence to: Christian G. Hübner3,6Dorothee Kern1 Correspondence and requests for materials should be addressed to D.K. (Email: dkern@brandeis.edu) or C.G.H. (Email: huebner@physik.uni-luebeck.de).

The mechanisms by which enzymes achieve extraordinary rate acceleration and specificity have long been of key interest in biochemistry. It is generally recognized that substrate binding coupled to conformational changes of the substrate–enzyme complex aligns the reactive groups in an optimal environment for efficient chemistry. Although chemical mechanisms have been elucidated for many enzymes, the question of how enzymes achieve the catalytically competent state has only recently become approachable by experiment and computation. Here we show crystallographic evidence for conformational substates along the trajectory towards the catalytically competent 'closed' state in the ligand-free form of the enzyme adenylate kinase. Molecular dynamics simulations indicate that these partially closed conformations are sampled in nanoseconds, whereas nuclear magnetic resonance and single-molecule fluorescence resonance energy transfer reveal rare sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale. Thus, the larger-scale motions in substrate-free adenylate kinase are not random, but preferentially follow the pathways that create the configuration capable of proficient chemistry. Such preferred directionality, encoded in the fold, may contribute to catalysis in many enzymes.

以上资料由西亚试剂：http://www.xiyashiji.com/ 提供此产品的详细信息如密度,含量,分子式,分子量等均可在西亚官网查询
相关产品如溴化汞硝酸亚汞氯化亚汞乙酸苯汞氯化钾汞碘化汞钾硫氰酸汞硫酸亚汞氧化汞氯化汞碘化汞硝酸汞三氯氧磷三氯化磷碘甲烷二碘甲烷三碘甲烷三氟碘甲烷氘代碘甲烷碘乙烷 1,2-二碘乙烷甲酸铷碘化铷溴化铷铬酸铷硫酸铷氟化铷硝酸铷氯化铷碳酸铷硫酸镱碳酸镱氯化镱硝酸镱氧化镱等均有销售.欢迎订购

上一篇：西亚试剂：Opposing microRNA families regulate self-renewal in mouse e
下一篇：西亚试剂：Cell：Y染色体的惊人发现