DevS, a Heme-Containing Two-Component Oxygen Sensor of Mycobacterium tuberculosis
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- 作者：Alexandra Ioanoviciu ; Erik T. Yukl ; Pierre Moë ; nne-Loccoz ; Paul R. Ortiz de Montellano
- 刊名：Biochemistry
- 出版年：2007
- 出版时间：April 10, 2007
- 年：2007
- 卷：46
- 期：14
- 页码：4250 - 4260
- 全文大小：198K
- 年卷期：v.46,no.14(April 10, 2007)
- ISSN：1520-4995
文摘
Mycobacterium tuberculosis can exist in the actively growing state of the overt disease or ina latent quiescent state that can be induced, among other things, by anaerobiosis. Eradication of the latentstate is particularly difficult with the available drugs and requires prolonged treatment. DevS is a memberof the DevS-DevR two-component regulatory system that is thought to mediate the cellular response toanaerobiosis. Here we report the cloning, expression, and initial characterization of a truncated version ofDevS (DevS642) containing only the N-terminal GAF sensor domain (GAF-A) and of the full-lengthprotein DevS. The DevS truncated construct quantitatively binds heme in a 1:1 stoichiometry, and thecomplex of the protein with ferrous heme reversibly binds O2, NO, and CO. UV-vis and resonanceRaman spectroscopy of the wild-type protein and the H149A mutant confirm that His149 is the proximalligand to the heme iron atom. While the heme-CO complex is present as two conformers in the GAF-Adomain, a single set of [Fe-C-O] vibrations is observed with the full-length protein, suggesting thatinteractions between domains within DevS influence the distal pocket environment of the heme in theGAF-A domain.