A Kinetic, Spectroscopic, and Redox Study of Human Tryptophan 2,3-Dioxygenase

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• 作者：Jaswir Basran ; Sara A. Rafice ; Nishma Chauhan ; Igor Efimov ; Myles R. Cheesman ; Lila Ghamsari ; Emma Lloyd Raven
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：April 22, 2008
• 年：2008
• 卷：47
• 期：16
• 页码：4752 - 4760
• 全文大小：391K
• 年卷期：v.47,no.16(April 22, 2008)
• ISSN：1520-4995

文摘

The family of heme dioxygenases, as exemplified by indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase, catalyzes the oxidative cleavage of L-tryptophan to N-formylkynurenine. Here, we describe a bacterial expression system for human tryptophan 2,3-dioxygenase (rhTDO) together with spectroscopic, kinetic, and redox analyses. We find unexpected differences between human tryptophan 2,3-dioxygenase and human indoleamine 2,3-dioxygenase [Chauhan et al. (2008) Biochemistry 47, 4761−4769]. Thus, in contrast to indoleamine 2,3-dioxygenase, the catalytic ferrous−oxy complex of rhTDO is not observed, nor does the enzyme discriminate against substrate binding to the ferric derivative. In addition, we show that the rhTDO is also catalytically active in the ferric form. These new findings illustrate that significant mechanistic differences exist across the heme dioxygenase family, and the data are discussed within this broader framework.