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Biochemistry. 2007 Apr 10;46(14):4250-60. Epub 2007 Mar 20.

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

Author information

1
Department of Pharmaceutical Chemistry, University of California, 600 16th Street, San Francisco, California 94158-2517, USA.

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.

PMID:
17371046
PMCID:
PMC2518089
DOI:
10.1021/bi602422p
[Indexed for MEDLINE]
Free PMC Article

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