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

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

Research output: Contribution to journalArticle

58 Citations (Scopus)

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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Oxygen sensors
Heme
Mycobacterium tuberculosis
Oxygen
Anaerobiosis
Carbon Monoxide
Proteins
Raman Spectrum Analysis
Cloning
Mutant Proteins
Vibration
Stoichiometry
Raman spectroscopy
Organism Cloning
Iron
Ligands
Atoms
Sensors
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry

Cite this

DevS, a heme-containing two-component oxygen sensor of Mycobacterium tuberculosis. / Ioanovichi, Alexandra; Yukl, Erik T.; Moenne-Loccoz, Pierre; Ortiz De Montellano, Paul R.

In: Biochemistry, Vol. 46, No. 14, 10.04.2007, p. 4250-4260.

Research output: Contribution to journalArticle

Ioanovichi, Alexandra ; Yukl, Erik T. ; Moenne-Loccoz, Pierre ; Ortiz De Montellano, Paul R. / DevS, a heme-containing two-component oxygen sensor of Mycobacterium tuberculosis. In: Biochemistry. 2007 ; Vol. 46, No. 14. pp. 4250-4260.
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