Inhibitory Substrate Binding Site of Human Indoleamine 2,3-Dioxygenase
نویسندگان
چکیده
منابع مشابه
The Mechanism of Substrate Inhibition in Human Indoleamine 2,3-Dioxygenase
Indoleamine 2,3-dioxygenase catalyzes the O(2)-dependent oxidation of L-tryptophan (L-Trp) to N-formylkynurenine (NFK) as part of the kynurenine pathway. Inhibition of enzyme activity at high L-Trp concentrations was first noted more than 30 years ago, but the mechanism of inhibition has not been established. Using a combination of kinetic and reduction potential measurements, we present eviden...
متن کاملLigand and substrate migration in human indoleamine 2,3-dioxygenase.
Human indoleamine 2,3-dioxygenase (hIDO), a monomeric heme enzyme, catalyzes the oxidative degradation of L-Trp and other indoleamine derivatives. Using Fourier transform infrared and optical absorption spectroscopy, we have investigated the interplay between ferrous hIDO, the ligand analog CO, and the physiological substrate L-Trp. These data provide the long sought evidence for two distinct L...
متن کاملThe heme environment of recombinant human indoleamine 2,3-dioxygenase. Structural properties and substrate-ligand interactions.
Indoleamine 2,3-dioxygenase is a heme enzyme that catalyzes the oxidative degradation of L-Trp and other indoleamines. We have used resonance Raman spectroscopy to characterize the heme environment of purified recombinant human indoleamine 2,3-dioxygenase (hIDO). In the absence of L-Trp, the spectrum of the Fe(3+) form displayed six-coordinate, mixed high and low spin character. Addition of L-T...
متن کاملAsp274 and his346 are essential for heme binding and catalytic function of human indoleamine 2,3-dioxygenase.
L-Tryptophan is the least abundant essential amino acid in humans. Indoleamine 2,3-dioxgyenase (IDO) is a cytosolic heme protein which, together with the hepatic enzyme tryptophan 2,3-dioxygenase, catalyzes the first and rate-limiting step in the major pathway of tryptophan metabolism, the kynurenine pathway. The physiological role of IDO is not fully understood but is of great interest, becaus...
متن کاملInduction of Indoleamine 2,3-Dioxygenase by Interferon- in Human Islets
Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial, rate-limiting step of tryptophan (Trp) catabolism along the kynurenine (KYN) pathway, and its induction in cells of the immune system in response to cytokines has been implicated in the regulation of antigen presentation and responses to cell-mediated immune attack. Microarray and quantitative PCR analyses of isolated human islets incubat...
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ژورنال
عنوان ژورنال: Journal of the American Chemical Society
سال: 2009
ISSN: 0002-7863,1520-5126
DOI: 10.1021/ja9029768