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Annu Rev Biochem. 2003;72:517-71. Epub 2003 Apr 10.

Challenges in enzyme mechanism and energetics.

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  • 1Department of Biochemistry, Stanford University, B400 Beckman Center, 279 Campus Drive, Stanford, California 94305-5307, USA. dkraut@stanford.edu

Abstract

Since the discovery of enzymes as biological catalysts, study of their enormous catalytic power and exquisite specificity has been central to biochemistry. Nevertheless, there is no universally accepted comprehensive description. Rather, numerous proposals have been presented over the past half century. The difficulty in developing a comprehensive description for the catalytic power of enzymes derives from the highly cooperative nature of their energetics, which renders impossible a simple division of mechanistic features and an absolute partitioning of catalytic contributions into independent and energetically additive components. Site-directed mutagenesis has emerged as an enormously powerful approach to probe enzymatic catalysis, illuminating many basic features of enzyme function and behavior. The emphasis of site-directed mutagenesis on the role of individual residues has also, inadvertently, limited experimental and conceptual attention to the fundamentally cooperative nature of enzyme function and energetics. The first part of this review highlights the structural and functional interconnectivity central to enzymatic catalysis. In the second part we ask: What are the features of enzymes that distinguish them from simple chemical catalysts? The answers are presented in conceptual models that, while simplified, help illustrate the vast amount known about how enzymes achieve catalysis. In the last section, we highlight the molecular and energetic questions that remain for future investigation and describe experimental approaches that will be necessary to answer these questions. The promise of advancing and integrating cutting edge conceptual, experimental, and computational tools brings mechanistic enzymology to a new era, one poised for novel fundamental insights into biological catalysis.

[PubMed - indexed for MEDLINE]
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