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| | ==STRUCTURE OF THE FIRST GAF DOMAIN E87G MUTANT OF MYCOBACTERIUM TUBERCULOSIS DOSS== | | ==STRUCTURE OF THE FIRST GAF DOMAIN E87G MUTANT OF MYCOBACTERIUM TUBERCULOSIS DOSS== |
| - | <StructureSection load='2y8h' size='340' side='right' caption='[[2y8h]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='2y8h' size='340' side='right'caption='[[2y8h]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2y8h]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y8H OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y8H FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2y8h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y8H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y8H FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2w3d|2w3d]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2y8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y8h OCA], [http://pdbe.org/2y8h PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y8h RCSB], [http://www.ebi.ac.uk/pdbsum/2y8h PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y8h ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2y8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y8h OCA], [https://pdbe.org/2y8h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y8h RCSB], [https://www.ebi.ac.uk/pdbsum/2y8h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y8h ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/DEVS_MYCTU 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).<ref>PMID:15033981</ref> <ref>PMID:18474359</ref> <ref>PMID:18400743</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myctu]] | + | [[Category: Large Structures]] |
| - | [[Category: Cho, H J]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Cho, H Y]] | + | [[Category: Cho HJ]] |
| - | [[Category: Kang, B S]] | + | [[Category: Cho HY]] |
| - | [[Category: Transferase]] | + | [[Category: Kang BS]] |
| 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]
Publication Abstract from PubMed
Two sensor kinases, DosS and DosT, are responsible for recognition of hypoxia in Mycobacterium tuberculosis. Both proteins are structurally similar to each other, but DosS is a redox sensor while DosT binds oxygen. The primary difference between the two proteins is the channel to the heme present in their GAF domains. DosS has a channel that is blocked by E87 while DosT has an open channel. Absorption spectra of DosS mutants with an open channel show that they bind oxygen as DosT does when they are exposed to air, while DosT G85E mutant is oxidized similarly to DosS without formation of an oxy-ferrous form. This suggests that oxygen accessibility to heme is the primary factor governing the oxygen-binding properties of these proteins.
Blockage of the channel to heme by the E87 side chain in the GAF domain of Mycobacterium tuberculosis DosS confers the unique sensitivity of DosS to oxygen.,Cho HY, Cho HJ, Kim MH, Kang BS FEBS Lett. 2011 Jun 23;585(12):1873-8. Epub 2011 Apr 27. PMID:21536032[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 MH, Kang BS. Blockage of the channel to heme by the E87 side chain in the GAF domain of Mycobacterium tuberculosis DosS confers the unique sensitivity of DosS to oxygen. FEBS Lett. 2011 Jun 23;585(12):1873-8. Epub 2011 Apr 27. PMID:21536032 doi:10.1016/j.febslet.2011.04.050
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