Inhibitory Substrate Binding Site of Human Indoleamine 2,3-Dioxygenase

被引：79

作者：

Lu, Changyuan ^{[1
]}

Lin, Yu ^{[1
]}

Yeh, Syun-Ru ^{[1
]}

机构：

[1] Yeshiva Univ Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2009年 / 131卷 / 36期

关键词：

TRYPTOPHAN-METABOLISM; EXIGUAMINE-A; OXYGEN; MECHANISM; ENZYMES; TARGET; IDO;

D O I：

10.1021/ja9029768

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Human indoleamine 2,3-dioxygenase (hIDO) is an intracellular heme-containing enzyme, which catalyzes the initial and rate-determining step of L-tryptophan (L-Trp) metabolism via the kynurenine pathway. Due to its immunosuppressive function, hIDO has been recognized as an important drug target for cancer. Here we report evidence supporting the presence of an inhibitory substrate binding site (S-i) in hIDO that is capable of binding molecules with a wide variety of structures, including substrates (L-Trp and 1-methyl-L-tryptophan), an effector (3-indole ethanol), and an uncompetitive inhibitor (Mitomycin C). The data offer useful guidelines for future development of more potent hIDO inhibitors; they also call for the re-evaluation of the action mechanism of Mitomycin C (MtoC), a widely used antitumor chemotherapeutic agent.

引用

页码：12866 / +

页数：3

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