Reassessment of the Reaction Mechanism in the Heme Dioxygenases

被引：61

作者：

Chauhan, Nishma ^{[2
]}

Thackray, Sarah J. ^{[1
]}

Rafice, Sara A. ^{[2
]}

Eaton, Graham ^{[2
]}

Lee, Michael ^{[2
]}

Efimov, Igor ^{[2
]}

Basran, Jaswir ^{[3
]}

Jenkins, Paul R. ^{[2
]}

Mowat, Christopher G. ^{[1
]}

Chapman, Stephen K. ^{[1
]}

Raven, Emma Lloyd ^{[2
]}

机构：

[1] Univ Edinburgh, Sch Chem, EaStCHEM, Edinburgh EH9 3JJ, Midlothian, Scotland

[2] Univ Leicester, Dept Chem, Leicester LE1 7RH, Leics, England

[3] Univ Leicester, Dept Biochem, Leicester LE1 9HN, Leics, England

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2009年 / 131卷 / 12期

基金：

英国惠康基金;

关键词：

HUMAN INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN; CATALYSIS;

D O I：

10.1021/ja808326g

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are heme enzymes that catalyze the O-2-dependent oxidation of L-tryptophan to N-formyl-kynurenine. Previous proposals for the mechanism of this reaction have suggested that deprotonation of the indole NH group, either by an active-site base or by oxygen bound to the heme iron, as the initial step. In this work, we have examined the activity of 1-Me-L-Trp with three different heme dioxygenases and their site-directed variants. We find, in contrast to previous work, that 1-Me-L-Trp is a substrate for the heme dioxygenase enzymes. These observations suggest that deprotonation of the indole N-1 is not essential for catalysis, and an alternative reaction mechanism, based on the known chemistry of indoles, is presented.

引用

页码：4186 / +

页数：3

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