Simulated 18O Kinetic Isotope Effects in Enzymatic Hydrolysis of Guanosine Triphosphate

被引：4

作者：

Nemukhin, A. V. ^{[1
,2
]}

Shadrina, M. S. ^{[1
]}

Grigorenko, B. L. ^{[1
]}

Du, X. ^{[3
]}

机构：

[1] Moscow MV Lomonosov State Univ, Fac Chem, Moscow 119991, Russia

[2] Russian Acad Sci, Emanuel Inst Biochem Phys, Moscow 119994, Russia

[3] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

来源：

BIOCHEMISTRY-MOSCOW | 2009年 / 74卷 / 09期

基金：

俄罗斯基础研究基金会;

关键词：

kinetic isotope effect; GTP hydrolysis; p21Ras; Ras-GAP; EF-Tu; GTP HYDROLYSIS; CATALYZED-HYDROLYSIS; PHOSPHORYL TRANSFER; RAS; MECHANISMS; PROTEINS; INSIGHTS;

D O I：

10.1134/S0006297909090132

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We compare the computed on the base of quantum mechanical-molecular mechanical (QM/MM) modeling kinetic isotope effects (KIEs) for a series of the O-18-labeled substrates in enzymatic hydrolysis of guanosine triphosphate (GTP) with those measured experimentally. Following the quantitative structure-activity relationship concept, we introduce the correlation between KIEs and structure of substrates with the help of a labeling index, which also aids better imaging of presentation of both experimental and theoretical data. An evident correlation of the computed and measured KIEs provides support to the predominantly dissociative-type reaction mechanism of enzymatic GTP hydrolysis predicted in QM/MM simulations.

引用

页码：1044 / 1048

页数：5

共 22 条

[1] Mechanistic alternatives phosphate monoester hydrolysis:: what conclusions can be drawn from available experimental data?
Åqvist, J
Kolmodin, K
Florian, J
Warshel, A
[J]. CHEMISTRY & BIOLOGY, 1999, 6 (03): : R71 - R80
[2] THE GTPASE SUPERFAMILY - A CONSERVED SWITCH FOR DIVERSE CELL FUNCTIONS
BOURNE, HR
SANDERS, DA
MCCORMICK, F
[J]. NATURE, 1990, 348 (6297) : 125 - 132
[3] Enzymatic GTP hydrolysis: Insights from an ab initio molecular dynamics study
Cavalli, A
Carloni, P
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (14) : 3763 - 3768
[4] The use of isotope effects to determine enzyme mechanisms
Cleland, WW
[J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2005, 433 (01) : 2 - 12
[5] A method to determine 18O kinetic isotope effects in the hydrolysis of nucleotide triphosphates
Du, Xinlin
Ferguson, Kurt
Gregory, Robert
Sprang, Stephen R.
[J]. ANALYTICAL BIOCHEMISTRY, 2008, 372 (02) : 213 - 221
[6] Kinetic isotope effects in Ras-catalyzed GTP hydrolysis: Evidence for a loose transition state
Du, XL
Black, GE
Lecchi, P
Abramson, FP
Sprang, SR
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (24) : 8858 - 8863
[7] How does GAP catalyze the GTPase reaction of Ras?:: A computer simulation study
Glennon, TM
Villà, J
Warshel, A
[J]. BIOCHEMISTRY, 2000, 39 (32) : 9641 - 9651
[8] The effective fragment potential method: A QM-based MM approach to modeling environmental effects in chemistry
Gordon, MS
Freitag, MA
Bandyopadhyay, P
Jensen, JH
Kairys, V
Stevens, WJ
[J]. JOURNAL OF PHYSICAL CHEMISTRY A, 2001, 105 (02) : 293 - 307
[9] Mechanism of the chemical step for the guanosine triphosphate (GTP) hydrolysis catalyzed by elongation factor Tu
Grigorenko, B. L.
Shadrina, M. S.
Topol, I. A.
Collins, J. R.
Nemukhin, A. V.
[J]. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2008, 1784 (12): : 1908 - 1917
[10] Mechanism of the myosin catalyzed hydrolysis of ATP as rationalized by molecular modeling
Grigorenko, Bella L.
Rogov, Alexander V.
Topol, Igor A.
Burt, Stanley K.
Martinez, Hugo M.
Nemukhin, Alexander V.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (17) : 7057 - 7061

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