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Science 29 August 2003:
Vol. 301. no. 5637, pp. 1196 - 1202
DOI: 10.1126/science.1085515
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Review

A Perspective on Enzyme Catalysis

Stephen J. Benkovic* and Sharon Hammes-Schiffer*

The seminal hypotheses proposed over the years for enzymatic catalysis are scrutinized. The historical record is explored from both biochemical and theoretical perspectives. Particular attention is given to the impact of molecular motions within the protein on the enzyme's catalytic properties. A case study for the enzyme dihydrofolate reductase provides evidence for coupled networks of predominantly conserved residues that influence the protein structure and motion. Such coupled networks have important implications for the origin and evolution of enzymes, as well as for protein engineering.

Department of Chemistry, 152 Davey Laboratory, Pennsylvania State University, University Park, PA 16802, USA.

* To whom correspondence should be addressed.E-mail: sjb1{at}psu.edu (S.J.B.) and shs{at}chem.psu.edu (S.H.S.)

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