Research Repository

The role of serine 167 in human indoleamine 2,3-dioxygenase: A comparison with tryptophan 2,3-dioxygenase

Chauhan, N and Basran, J and Efimov, I and Svistunenko, DA and Seward, HE and Moody, PCE and Raven, EL (2008) 'The role of serine 167 in human indoleamine 2,3-dioxygenase: A comparison with tryptophan 2,3-dioxygenase.' Biochemistry, 47 (16). 4761 - 4769. ISSN 0006-2960

Full text not available from this repository.

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 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 -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. © 2008 American Chemical Society. 2 2

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 09 Oct 2011 07:36
Last Modified: 07 Apr 2021 10:15
URI: http://repository.essex.ac.uk/id/eprint/987

Actions (login required)

View Item View Item