Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/13327
Title: The role of serine 167 in human indoleamine 2,3-dioxygenase: a comparison with tryptophan 2,3-dioxygenase.
Authors: Chauhan, N
Basran, J
Efimov, I
Svistunenko, DA
Seward, HE
Moody, PC
Raven, EL
First Published: 22-Apr-2008
Citation: BIOCHEMISTRY, 2008, 47 (16), pp. 4761-4769
Abstract: The initial step in the l-kynurenine pathway is oxidation of l-tryptophan to N-formylkynurenine and is catalyzed by one of two heme enzymes, tryptophan 2,3-dioxygenase (TDO) or indoleamine 2,3-dioxygenase (IDO). Here, we address the role of the conserved active site Ser167 residue in human IDO (S167A and S167H variants), which is replaced with a histidine in other mammalian and bacterial TDO enzymes. Our kinetic and spectroscopic data for S167A indicate that this residue is not essential for O 2 or substrate binding, and we propose that hydrogen bond stabilization of the catalytic ferrous-oxy complex involves active site water molecules in IDO. The data for S167H show that the ferrous-oxy complex is dramatically destabilized in this variant, which is similar to the behavior observed in human TDO [Basran et al. (2008) Biochemistry 47, 4752-4760], and that this destabilization essentially destroys catalytic activity. New kinetic data for the wild-type enzyme also identify the ternary [enzyme-O 2-substrate] complex. The data reveal significant differences between the IDO and TDO enzymes, and the implications of these results are discussed in terms of our current understanding of IDO and TDO catalysis.
DOI Link: 10.1021/bi702405a
ISSN: 0006-2960
Links: http://hdl.handle.net/2381/13327
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Chemistry

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