The kynurenine pathway is the major route of tryptophan metabolism. The first step of this pathway is catalysed by one of two heme-dependent dioxygenase enzymes - tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) - leading initially to the formation of N-formylkynurenine (NFK). In this paper, we present a crystal structure of a bacterial TDO from X. campestris in complex with l-kynurenine, the hydrolysed product of NFK. l-kynurenine is bound at the active site in a similar location to the substrate (l-Trp). Hydrogen bonding interactions with Arg117 and the heme 7-propionate anchor the l-kynurenine molecule into the pocket. A mechanism for the hydrolysis of NFK in the active site is presented.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jinorgbio.2021.111604 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mutation of cysteine residues alters the heme-binding pocket of indoleamine 2,3-dioxygenase-1.
Biochem Biophys Res Commun
July 2013
Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, Australia.
The hemoprotein indoleamine 2,3-dioxygenase-1 (IDO1) is the first and rate-limiting enzyme in mammalian tryptophan metabolism. Interest in IDO1 continues to grow, due to the ever expanding influence IDO1 plays in the immune response. This study examined the contribution of all individual cysteine residues towards the overall catalytic properties and stability of recombinant human IDO1 via mutagenesis studies using a range of biochemical and spectroscopic techniques, including in vitro kinetic assessment, secondary structure identification via circular dichroism spectroscopy and thermal stability assessment.
View Article and Find Full Text PDFTreatment of ME180 cells with interferon-gamma causes apoptosis as a result of tryptophan starvation.
J Interferon Cytokine Res
September 1996
Department of Biology, Indiana University, Bloomington, USA.
Indoleamine 2'3 dioxygenase (INDO), the rate-limiting enzyme in the catabolism of the essential amino acid L-tryptophan, is induced in many cell lines following interferon gamma (IFN-gamma) treatment. The induction of this enzyme has been associated with the antiparasitic and cytotoxic activities of human IFN-gamma. DNA analysis coupled to morphologic studies indicated that ME180 cells underwent apoptosis within 48 h of treatment with IFN-gamma.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!