Crystal Structure and Mechanism of Tryptophan 2,3-Dioxygenase, a Heme Enzyme Involved in Tryptophan Catabolism and in Quinolinate Biosynthesis

Journal Article · Mon Jan 01 04:00:00 EST 2007 · Biochemistry

DOI:https://doi.org/10.1021/bi0620095· OSTI ID:930261

Zhang, Y; Kang, S; Mukherjee, T; Bale, S; Crane, B; Begley, T; Ealick, S

The structure of tryptophan 2,3-dioxygenase (TDO) from Ralstonia metallidurans was determined at 2.4 {angstrom}. 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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 930261
• Report Number(s): BNL--80953-2008-JA
• Journal Information: Biochemistry, Journal Name: Biochemistry Vol. 46; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
BIOSYNTHESIS
CATABOLISM
CRYSTAL STRUCTURE
ENZYMES
HEME
KYNURENINE
MUTAGENESIS
OXIDATION
SIMULATION
SUBSTRATES
TOLERANCE
TRYPTOPHAN
national synchrotron light source