Crystal Structure and Mechanism of Tryptophan 2,3-Dioxygenase, a Heme Enzyme Involved in Tryptophan Catabolism and in Quinolinate Biosynthesis

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• 作者：Yang Zhang ; Seong A. Kang ; Tathagata Mukherjee ; Shridhar Bale ; Brian R. Crane ; Tadhg P. Begley ; Steven E. Ealick
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：January 9, 2007
• 年：2007
• 卷：46
• 期：1
• 页码：145 - 155
• 全文大小：720K
• 年卷期：v.46,no.1(January 9, 2007)
• ISSN：1520-4995

文摘

The structure of tryptophan 2,3-dioxygenase (TDO) from Ralstonia metallidurans wasdetermined at 2.4 Å. TDO catalyzes the irreversible oxidation of L-tryptophan to N-formyl kynurenine,which is the initial step in tryptophan catabolism. TDO is a heme-containing enzyme and is highly specificfor its substrate L-tryptophan. The structure is a tetramer with a heme cofactor bound at each active site.The monomeric fold, as well as the heme binding site, is similar to that of the large domain of indoleamine2,3-dioxygenase, an enzyme that catalyzes the same reaction except with a broader substrate tolerance.Modeling of the putative (S)-tryptophan hydroperoxide intermediate into the active site, as well as substrateanalogue and mutagenesis studies, are consistent with a Criegee mechanism for the reaction.