Two-state reactivity mechanisms of hydroxylation and epoxidation by cytochrome P-450 revealed by theory

被引:296
作者
Shaik, S [1 ]
de Visser, SP
Ogliaro, F
Schwarz, H
Schröder, D
机构
[1] Hebrew Univ Jerusalem, Dept Organ Chem, IL-91904 Jerusalem, Israel
[2] Hebrew Univ Jerusalem, Lise Meitner Minerva Ctr Computat Quantum Chem, IL-91904 Jerusalem, Israel
[3] Tech Univ Berlin, Inst Chem, D-10623 Berlin, Germany
基金
以色列科学基金会;
关键词
D O I
10.1016/S1367-5931(02)00363-0
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
Recent Computational studies of alkane hydroxylation and alkene epoxidation by a model active species of the enzyme cytochrome P-450 reveal a two-state reactivity (TSR) scenario in which the information content of the product distribution is determined jointly by two states. TSR is used to reconcile the dilemma of the consensus 'rebound mechanism' of alkane hydroxylation, which emerged from experimental studies of ultra-fast radical clocks. The dilemma, stated succinctly as 'radicals are both present and absent and the rebound mechanism is both right and wrong, is simply understood once one is cognizant that the mechanism operates by two states, one low-spin (LS) the other high-spin (HS). In both states, bond activation proceeds in a manner akin to the rebound mechanism, but the LS mechanism is effectively concerted, whereas the HS is stepwise with incursion of radical intermediates.
引用
收藏
页码:556 / 567
页数:12
相关论文
共 77 条
[71]  
VOLZ TJ, 2002, IN PRESS J AM CHEM S, V124
[72]   Synthetic active site analogues of heme-thiolate proteins -: Characterization and identification of intermediates of the catalytic cycles of cytochrome P450cam and chloroperoxidase [J].
Woggon, WD ;
Wagenknecht, HA ;
Claude, C .
JOURNAL OF INORGANIC BIOCHEMISTRY, 2001, 83 (04) :289-300
[73]  
WOGGON WD, 1996, TOP CURR CHEM, V184, P40
[74]   Roles of the axial push effect in cytochrome P450cam studied with the site-directed mutagenesis at the heme proximal site [J].
Yoshioka, S ;
Takahashi, S ;
Ishimori, K ;
Morishima, I .
JOURNAL OF INORGANIC BIOCHEMISTRY, 2000, 81 (03) :141-151
[75]   A theoretical study of the dynamic behavior of alkane hydroxylation by a compound I model of cytochrome P450 [J].
Yoshizawa, K ;
Kamachi, T ;
Shiota, Y .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (40) :9806-9816
[76]   Reaction paths for the conversion of methane to methanol catalyzed by FeO+ [J].
Yoshizawa, K ;
Shiota, Y ;
Yamabe, T .
CHEMISTRY-A EUROPEAN JOURNAL, 1997, 3 (07) :1160-1169
[77]   Kinetic isotope effects in a C-H bond dissociation by the iron-oxo species of cytochrome P450 [J].
Yoshizawa, K ;
Kagawa, Y ;
Shiota, Y .
JOURNAL OF PHYSICAL CHEMISTRY B, 2000, 104 (51) :12365-12370