DevS, a heme-containing two-component oxygen sensor of Mycobacterium tuberculosis

Alexandra Ioanovichi, Erik T. Yukl, Pierre Moënne-Loccoz, Paul R. Ortiz De Montellano

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Abstract

Mycobacterium tuberculosis can exist in the actively growing state of the overt disease or in a latent quiescent state that can be induced, among other things, by anaerobiosis. Eradication of the latent state is particularly difficult with the available drugs and requires prolonged treatment. DevS is a member of the DevS-DevR two-component regulatory system that is thought to mediate the cellular response to anaerobiosis. Here we report the cloning, expression, and initial characterization of a truncated version of DevS (DevS642) containing only the N-terminal GAF sensor domain (GAF-A) and of the full-length protein DevS. The DevS truncated construct quantitatively binds heme in a 1:1 stoichiometry, and the complex of the protein with ferrous heme reversibly binds O2, NO, and CO. UV-vis and resonance Raman spectroscopy of the wild-type protein and the H149A mutant confirm that His149 is the proximal ligand to the heme iron atom. While the heme-CO complex is present as two conformers in the GAF-A domain, a single set of [Fe-C-O] vibrations is observed with the full-length protein, suggesting that interactions between domains within DevS influence the distal pocket environment of the heme in the GAF-A domain.

Original languageEnglish (US)
Pages (from-to)4250-4260
Number of pages11
JournalBiochemistry
Volume46
Issue number14
DOIs
StatePublished - Apr 10 2007

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ASJC Scopus subject areas

  • Biochemistry

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