期刊
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 82
卷 82, 期 -, 页码 471-496出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-biochem-051710-133623
关键词
enzyme catalysis; hydrogen tunneling; protein dynamics
资金
- National Institutes of Health [GM025765, GM65368]
- National Science Foundation [MCB0446395, CHE-1149023]
- United States-Israel Binational Science Foundation [2007256]
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1149023] Funding Source: National Science Foundation
- Division of Computing and Communication Foundations
- Direct For Computer & Info Scie & Enginr [2007256] Funding Source: National Science Foundation
The relationship between protein dynamics and function is a subject of considerable contemporary interest. Although protein motions are frequently observed during ligand binding and release steps, the contribution of protein motions to the catalysis of bond making/breaking processes is more difficult to probe and verify. Here, we show how the quantum mechanical hydrogen tunneling associated with enzymatic C-H bond cleavage provides a unique window into the necessity of protein dynamics for achieving optimal catalysis. Experimental findings support a hierarchy of thermodynamically equilibrated motions that control the H-donor and -acceptor distance and active-site electrostatics, creating an ensemble of conformations suitable for H-tunneling. A possible extension of this view to methyl transfer and other catalyzed reactions is also presented. The impact of understanding these dynamics on the conceptual framework for enzyme activity, inhibitor/drug design, and biomimetic catalyst design is likely to be substantial.
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