Structure and Reaction Mechanism in the Heme Dioxygenases

• Published in: Biochemistry (Easton) Vol. 50; no. 14; pp. 2717 - 2724
• Main Authors: Efimov, Igor, Basran, Jaswir, Thackray, Sarah J, Handa, Sandeep, Mowat, Christopher G, Raven, Emma Lloyd
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 12-04-2011
• Subjects: Animals; Biocatalysis; Current Topic; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase - chemistry; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Kynurenine - analogs & derivatives; Kynurenine - chemistry; Kynurenine - metabolism; Models, Molecular; Molecular Structure; Protein Structure, Tertiary; Tryptophan - chemistry; Tryptophan - metabolism; Tryptophan Oxygenase - chemistry; Tryptophan Oxygenase - metabolism
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi101732n

As members of the family of heme-dependent enzymes, the heme dioxygenases are differentiated by virtue of their ability to catalyze the oxidation of l-tryptophan to N-formylkynurenine, the first and rate-limiting step in tryptophan catabolism. In the past several years, there have been a number of important developments that have meant that established proposals for the reaction mechanism in the heme dioxygenases have required reassessment. This focused review presents a summary of these recent advances, written from a structural and mechanistic perspective. It attempts to present answers to some of the long-standing questions, to highlight as yet unresolved issues, and to explore the similarities and differences of other well-known catalytic heme enzymes such as the cytochromes P450, NO synthase, and peroxidases.