Network of coupled promoting motions in enzyme catalysis

被引：385

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

共 31 条

[1] Hydride transfer in liver alcohol dehydrogenase: Quantum dynamics, kinetic isotope effects, and role of enzyme motion
Billeter, SR
Webb, SP
Agarwal, PK
Iordanov, T
Hammes-Schiffer, S
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (45) : 11262 - 11272
[2] Hybrid approach for including electronic and nuclear quantum effects in molecular dynamics simulations of hydrogen transfer reactions in enzymes
Billeter, SR
Webb, SP
Iordanov, T
Agarwal, PK
Hammes-Schiffer, S
[J]. JOURNAL OF CHEMICAL PHYSICS, 2001, 114 (15) : 6925 - 6936
[3] BOYS FS, 1966, QUANTUM THEORY ATOMS, P253
[4] Chemical basis for enzyme catalysis
Bruice, TC
Benkovic, SJ
[J]. BIOCHEMISTRY, 2000, 39 (21) : 6267 - 6274
[5] Evidence for a functional role of the dynamics of glycine-121 of Escherichia coli dihydrofolate reductase obtained from kinetic analysis of a site-directed mutant
Cameron, CE
Benkovic, SJ
[J]. BIOCHEMISTRY, 1997, 36 (50) : 15792 - 15800
[6] DETERMINATION BY RAMAN-SPECTROSCOPY OF THE PK(A), OF N5 OF DIHYDROFOLATE BOUND TO DIHYDROFOLATE-REDUCTASE - MECHANISTIC IMPLICATIONS
CHEN, YQ
KRAUT, J
BLAKLEY, RL
CALLENDER, R
[J]. BIOCHEMISTRY, 1994, 33 (23) : 7021 - 7026
[7] Energetically most likely substrate and active-site protonation sites and pathways in the catalytic mechanism of dihydrofolate reductase
Cummins, PL
Gready, JE
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (15) : 3418 - 3428
[8] DYNAMICS OF THE DIHYDROFOLATE-REDUCTASE FOLATE COMPLEX - CATALYTIC SITES AND REGIONS KNOWN TO UNDERGO CONFORMATIONAL CHANGE EXHIBIT DIVERSE DYNAMICAL FEATURES
EPSTEIN, DM
BENKOVIC, SJ
WRIGHT, PE
[J]. BIOCHEMISTRY, 1995, 34 (35) : 11037 - 11048
[9] DYNAMICS OF A FLEXIBLE LOOP IN DIHYDROFOLATE-REDUCTASE FROM ESCHERICHIA-COLI AND ITS IMPLICATION FOR CATALYSIS
FALZONE, CJ
WRIGHT, PE
BENKOVIC, SJ
[J]. BIOCHEMISTRY, 1994, 33 (02) : 439 - 442
[10] CONSTRUCTION AND EVALUATION OF THE KINETIC SCHEME ASSOCIATED WITH DIHYDROFOLATE-REDUCTASE FROM ESCHERICHIA-COLI
FIERKE, CA
JOHNSON, KA
BENKOVIC, SJ
[J]. BIOCHEMISTRY, 1987, 26 (13) : 4085 - 4092

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