Structural highlights
Function
DEVS_MYCTU Member of the two-component regulatory system DevR/DevS (DosR/DosS) involved in onset of the dormancy response. May act as a redox sensor (rather than a direct hypoxia sensor); the normal (aerobic growth) state is the Fe(3+) form, while the reduced (anaerobic growth) Fe(2+) form is probably active for phosphate transfer. It is probably reduced by flavin nucleotides such as FMN and FAD. May be the primary sensor for CO. Donates a phosphate group to DevR (DosR).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Mycobacterium tuberculosis is thought to undergo transformation into its non-replicating persistence state under the influence of hypoxia or nitric oxide (NO). This transformation is thought to be mediated via two sensor histidine kinases, DosS and DosT, each of which contains two GAF domains that are responsible for detecting oxygen tension. In this study we determined the crystal structures of the first GAF domain (GAF-A) of DosS, which shows an interaction with a heme. A b-type heme was embedded in a hydrophobic cavity of the GAF-A domain and was roughly perpendicular to the beta-sheet of the GAF domain. The heme iron was liganded by His-149 at the proximal heme axial position. The iron, in the oxidized form, was six-coordinated with a water molecule at the distal position. Upon reduction, the iron, in ferrous form, was five-coordinated, and when the GAF domain was exposed to atmospheric O(2), the ferrous form was oxidized to generate the Met form rather than a ferrous O(2)-bound form. Because the heme is isolated inside the GAF domain, its accessibility is restricted. However, a defined hydrogen bond network found at the heme site could accelerate the electron transferability and would explain why DosS was unable to bind O(2). Flavin nucleotides were shown to reduce the heme iron of DosS while NADH was unable to do so. These results suggest that DosS is a redox sensor and detects hypoxic conditions by its reduction.
Structural insight into the heme-based redox sensing by DosS from Mycobacterium tuberculosis.,Cho HY, Cho HJ, Kim YM, Oh JI, Kang BS J Biol Chem. 2009 May 8;284(19):13057-67. Epub 2009 Mar 10. PMID:19276084[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Roberts DM, Liao RP, Wisedchaisri G, Hol WG, Sherman DR. Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis. J Biol Chem. 2004 May 28;279(22):23082-7. Epub 2004 Mar 19. PMID:15033981 doi:10.1074/jbc.M401230200
- ↑ Shiloh MU, Manzanillo P, Cox JS. Mycobacterium tuberculosis senses host-derived carbon monoxide during macrophage infection. Cell Host Microbe. 2008 May 15;3(5):323-30. doi: 10.1016/j.chom.2008.03.007. PMID:18474359 doi:10.1016/j.chom.2008.03.007
- ↑ Kumar A, Deshane JS, Crossman DK, Bolisetty S, Yan BS, Kramnik I, Agarwal A, Steyn AJ. Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium tuberculosis dormancy regulon. J Biol Chem. 2008 Jun 27;283(26):18032-9. doi: 10.1074/jbc.M802274200. Epub 2008 , Apr 9. PMID:18400743 doi:10.1074/jbc.M802274200
- ↑ Cho HY, Cho HJ, Kim YM, Oh JI, Kang BS. Structural insight into the heme-based redox sensing by DosS from Mycobacterium tuberculosis. J Biol Chem. 2009 May 8;284(19):13057-67. Epub 2009 Mar 10. PMID:19276084 doi:10.1074/jbc.M808905200
