Network of coupled promoting motions in enzyme catalysis

被引：387

作者：

Agarwal, PK ^{[1
]}

Billeter, SR ^{[1
]}

Rajagopalan, PTR ^{[1
]}

Benkovic, SJ ^{[1
]}

Hammes-Schiffer, S ^{[1
]}

机构：

[1] Penn State Univ, Dept Chem, Davey Lab 152, University Pk, PA 16802 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2002年 / 99卷 / 05期

关键词：

D O I：

10.1073/pnas.052005999

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized. The present identification is based on genomic analysis for sequence conservation, kinetic measurements of multiple mutations, and mixed quantum/classical molecular dynamics simulations of hydride transfer. The motions in this network span time scales of femtoseconds to milliseconds and are found on the exterior of the enzyme as well as in the active site. This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site.

引用

页码：2794 / 2799

页数：6

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