Chauhan, Nishma and Basran, Jaswir and Efimov, Igor and Svistunenko, Dimitri A and Seward, Harriet E and Moody, Peter CE and Raven, Emma Lloyd (2008) The Role of Serine 167 in Human Indoleamine 2,3-Dioxygenase: A Comparison with Tryptophan 2,3-Dioxygenase. Biochemistry, 47 (16). pp. 4761-4769. DOI https://doi.org/10.1021/bi702405a
Chauhan, Nishma and Basran, Jaswir and Efimov, Igor and Svistunenko, Dimitri A and Seward, Harriet E and Moody, Peter CE and Raven, Emma Lloyd (2008) The Role of Serine 167 in Human Indoleamine 2,3-Dioxygenase: A Comparison with Tryptophan 2,3-Dioxygenase. Biochemistry, 47 (16). pp. 4761-4769. DOI https://doi.org/10.1021/bi702405a
Chauhan, Nishma and Basran, Jaswir and Efimov, Igor and Svistunenko, Dimitri A and Seward, Harriet E and Moody, Peter CE and Raven, Emma Lloyd (2008) The Role of Serine 167 in Human Indoleamine 2,3-Dioxygenase: A Comparison with Tryptophan 2,3-Dioxygenase. Biochemistry, 47 (16). pp. 4761-4769. DOI https://doi.org/10.1021/bi702405a
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<inf>2</inf> 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<inf>2</inf>-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.
Item Type: | Article |
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Uncontrolled Keywords: | Humans; Cyanides; Ferrous Compounds; Tryptophan Oxygenase; Tryptophan; Serine; Spectrophotometry; Electron Spin Resonance Spectroscopy; Binding Sites; Molecular Structure; Protein Binding; Substrate Specificity; Oxidation-Reduction; Mutation; Catalysis; Hydrogen Bonding; Thermodynamics; Models, Molecular; Indoleamine-Pyrrole 2,3,-Dioxygenase |
Subjects: | Q Science > QH Natural history > QH301 Biology |
Divisions: | Faculty of Science and Health Faculty of Science and Health > Life Sciences, School of |
SWORD Depositor: | Unnamed user with email elements@essex.ac.uk |
Depositing User: | Unnamed user with email elements@essex.ac.uk |
Date Deposited: | 09 Oct 2011 07:36 |
Last Modified: | 11 Jun 2025 12:01 |
URI: | http://repository.essex.ac.uk/id/eprint/987 |