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

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.