Crystal structure and mechanism of tryptophan 2,3-dioxygenase, a heme enzyme involved in tryptophan catabolism and in quinolinate biosynthesis. Academic Article uri icon

abstract

  • The structure of tryptophan 2,3-dioxygenase (TDO) from Ralstonia metallidurans was determined at 2.4 A. TDO catalyzes the irreversible oxidation of l-tryptophan to N-formyl kynurenine, which is the initial step in tryptophan catabolism. TDO is a heme-containing enzyme and is highly specific for its substrate l-tryptophan. The structure is a tetramer with a heme cofactor bound at each active site. The monomeric fold, as well as the heme binding site, is similar to that of the large domain of indoleamine 2,3-dioxygenase, an enzyme that catalyzes the same reaction except with a broader substrate tolerance. Modeling of the putative (S)-tryptophan hydroperoxide intermediate into the active site, as well as substrate analogue and mutagenesis studies, are consistent with a Criegee mechanism for the reaction.

published proceedings

  • Biochemistry

author list (cited authors)

  • Zhang, Y., Kang, S. A., Mukherjee, T., Bale, S., Crane, B. R., Begley, T. P., & Ealick, S. E.

citation count

  • 95

complete list of authors

  • Zhang, Yang||Kang, Seong A||Mukherjee, Tathagata||Bale, Shridhar||Crane, Brian R||Begley, Tadhg P||Ealick, Steven E

publication date

  • January 2007