Binding of l-kynurenine to X. campestris tryptophan 2,3-dioxygenase

J Inorg Biochem. 2021 Dec:225:111604. doi: 10.1016/j.jinorgbio.2021.111604. Epub 2021 Sep 16.

Abstract

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.

Keywords: Heme; Kynurenine; Tryptophan 2,3-dioxygenase.

MeSH terms

  • Hydrogen Bonding
  • Iron / chemistry
  • Kynurenine / chemistry
  • Kynurenine / metabolism*
  • Oxidation-Reduction
  • Protein Binding
  • Stereoisomerism
  • Tryptophan / chemistry
  • Tryptophan Oxygenase / chemistry
  • Tryptophan Oxygenase / metabolism*
  • Xanthomonas campestris / enzymology

Substances

  • Kynurenine
  • Tryptophan
  • Iron
  • Tryptophan Oxygenase