A new way to degrade heme: The mycobacterium tuberculosis enzyme MhuD catalyzes heme degradation without generating CO

Shusuke Nambu, Toshitaka Matsui, Celia W. Goulding, Satoshi Takahashi, Masao Ikeda-Saito

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

MhuD is an oxygen-dependent heme-degrading enzyme from Mycobacterium tuberculosis with high sequence similarity (∼45%) to Staphylococcus aureus IsdG and IsdI. Spectroscopic and mutagenesis studies indicate that the catalytically active 1:1 heme-MhuD complex has an active site structure similar to those of IsdG and IsdI, including the nonplanarity (ruffling) of the heme group bound to the enzyme. Distinct from the canonical heme degradation, we have found that the MhuD catalysis does not generate CO. Product analyses by electrospray ionization-MS and NMR show that MhuD cleaves heme at the β-meso position but retains the meso-carbon atom at the cleavage site, which is removed by canonical heme oxygenases. The novel tetrapyrrole product of MhuD, termed "mycobilin," has an aldehyde group at the cleavage site and a carbonyl group at either theβ-meso or theδ-meso position. Consequently, MhuD catalysis does not involve verdoheme, the key intermediate of ring cleavage by canonical heme oxygenase enzymes. Ruffled heme is apparently responsible for the heme degradation mechanism unique to MhuD. In addition, MhuD heme degradation without CO liberation is biologically significant as one of the signals of M. tuberculosis transition to dormancy is mediated by the production of host CO.

Original languageEnglish
Pages (from-to)10101-10109
Number of pages9
JournalJournal of Biological Chemistry
Volume288
Issue number14
DOIs
Publication statusPublished - 2013 Apr 5

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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