The effect of heme environment on the hydrogen abstraction reaction of camphor in P450cam catalysis:: A QM/MM study

被引：90

作者：

Altun, A

Guallar, V

Friesner, RA

Shaik, S

Thiel, W

机构：

[1] Max Planck Inst Kohlenforsch, D-45470 Mulheim, Germany

[2] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63108 USA

[3] Univ Nacl Colombia, Dept Chem, New York, NY 10027 USA

[4] Univ Nacl Colombia, Ctr Biomol Simulat, New York, NY 10027 USA

[5] Hebrew Univ Jerusalem, Dept Organ Chem, IL-91904 Jerusalem, Israel

[6] Hebrew Univ Jerusalem, Lise Meitner Minerva Ctr Computat Quantum Chem, IL-91904 Jerusalem, Israel

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2006年 / 128卷 / 12期

关键词：

D O I：

10.1021/ja058196w

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The discrepancies between the published QM/MM studies (Schöneboom, J. C.; Cohen, S.; Lin, H.; Shaik, S.; Thiel, W. J. Am. Chem. Soc. 2004, 126, 4017; Guallar, V.; Friesner, R. A. J. Am. Chem. Soc. 2004, 126, 8501) on H-abstraction of camphor in P450cam have largely been resolved. The crystallographic water molecule 903 situated near the oxo atom of Compound I acts as a catalyst for H-abstraction, lowering the barrier by about 4 kcal/mol. Spin density at the A-propionate side chain of heme can occur in the case of incomplete screening but has no major effect on the computed barrier. Copyright © 2006 American Chemical Society.

引用

收藏

页码：3924 / 3925

页数：2

相关论文

共 13 条

[1] Electronic structure of compound I in human isoforms of cytochrome P450 from QM/MM modeling [J].

Bathelt, CM ;

Zurek, J ;

Mulholland, AJ ;

Harvey, JN .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (37) :12900-12908

[2] Cytochrome P450CAM enzymatic catalysis cycle: A quantum mechanics molecular mechanics study [J].

Guallar, V ;

Friesner, RA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (27) :8501-8508

[3] Peripheral heme substituents control the hydrogen-atom abstraction chemistry in cytochromes P450 [J].

Guallar, V ;

Baik, MH ;

Lippard, SJ ;

Friesner, RA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (12) :6998-7002

[4]

GUALLAR V, IN PRESS J INORG BIO

[5] Exceptionally stable salt bridges in cytochrome P450cam have functional roles [J].

Lounnas, V ;

Wade, RC .

BIOCHEMISTRY, 1997, 36 (18) :5402-5417

[6] All-atom empirical potential for molecular modeling and dynamics studies of proteins [J].

MacKerell, AD ;

Bashford, D ;

Bellott, M ;

Dunbrack, RL ;

Evanseck, JD ;

Field, MJ ;

Fischer, S ;

Gao, J ;

Guo, H ;

Ha, S ;

Joseph-McCarthy, D ;

Kuchnir, L ;

Kuczera, K ;

Lau, FTK ;

Mattos, C ;

Michnick, S ;

Ngo, T ;

Nguyen, DT ;

Prodhom, B ;

Reiher, WE ;

Roux, B ;

Schlenkrich, M ;

Smith, JC ;

Stote, R ;

Straub, J ;

Watanabe, M ;

Wiórkiewicz-Kuczera, J ;

Yin, D ;

Karplus, M .

JOURNAL OF PHYSICAL CHEMISTRY B, 1998, 102 (18) :3586-3616

[7] Medium polarization and hydrogen bonding effects on compound I of Cytochrome p450: What kind of a radical is it really? [J].

Ogliaro, F ;

Cohen, S ;

de Visser, SP ;

Shaik, S .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (51) :12892-12893

[8]

Ortiz de Montellano PR, 2004, CYTOCHROME P450 STRU

[9] The catalytic pathway of cytochrome P450cam at atomic resolution [J].

Schlichting, I ;

Berendzen, J ;

Chu, K ;

Stock, AM ;

Maves, SA ;

Benson, DE ;

Sweet, BM ;

Ringe, D ;

Petsko, GA ;

Sligar, SG .

SCIENCE, 2000, 287 (5458) :1615-1622

[10] The elusive oxidant species of cytochrome P450 enzymes:: Characterization by combined quantum mechanical/molecular mechanical (QM/MM) calculations [J].

Schöneboom, JC ;

Lin, H ;

Reuter, N ;

Thiel, W ;

Cohen, S ;

Ogliaro, F ;

Shaik, S .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (27) :8142-8151