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New Concepts in Biochemistry

Free-Energy Landscape of Enzyme Catalysis^†

Stephen J. Benkovic^‡, Gordon G. Hammes*^§ and Sharon Hammes-Schiffer^‡

Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, and Department of Biochemistry, Box 3711, Duke University, Durham, North Carolina 27710

Biochemistry, 2008, 47 (11), pp 3317–3321

DOI: 10.1021/bi800049z

Publication Date (Web): February 26, 2008

†

This work was supported by Grants GM56207 (to S.H.-S.) and GM073089 (to S.J.B.) from the National Institutes of Health (NIH).

‡

The Pennsylvania State University.

* To whom correspondence should be addressed: Telephone: (919) 684-8848 . Fax: (919) 684-8885. E-mail: hamme001@mc.duke.edu.

Duke University.

Abstract

The concept is developed that enzyme mechanisms should be viewed as “catalytic networks” with multiple conformations that occur serially and in parallel in the mechanism. These coupled ensembles of conformations require a multi-dimensional standard free-energy surface that is very “rugged”, containing multiple minima and transition states. Experimental and theoretical evidence is presented to support this concept.

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PDB: 1rx2

History

Published In Issue March 18, 2008
Article ASAPFebruary 26, 2008
Received: January 09, 2008
Revised: February 06, 2008

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New Concepts in Biochemistry

Free-Energy Landscape of Enzyme Catalysis^†