How is the distal pocket of a heme protein optimized for binding of tryptophan?

Indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase catalyze the O(2) -dependent oxidation of l-tryptophan to N-formylkynurenine. Both are heme-containing enzymes, with a proximal histidine ligand, as found in the globins and peroxidases. From the structural information available so far, the distal heme pockets of these enzymes can contain a histidine residue (in tryptophan 2,3-dioxygenases), an arginine residue and numerous hydrophobic residues that line the pocket.

Oxidation of L-tryptophan in biology: a comparison between tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase.

The family of haem dioxygenases catalyse the initial oxidative cleavage of L-tryptophan to N-formylkynurenine, which is the first, rate-limiting, step in the L-kynurenine pathway. In the present paper, we discuss and compare structure and function across the family of haem dioxygenases by focusing on TDO (tryptophan 2,3-dioxygenase) and IDO (indoleamine 2,3-dioxygenase), including a review of recent structural information for both enzymes. The present paper describes how the recent development of recombinant expression systems has informed our more detailed understanding of the substrate binding, catalytic activity and mechanistic properties of these haem dioxygenases.

Reassessment of the reaction mechanism in the heme dioxygenases.

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.

A kinetic, spectroscopic, and redox study of human tryptophan 2,3-dioxygenase.

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.