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| | ==PknB-phosphorylated Rv1827== | | ==PknB-phosphorylated Rv1827== |
| - | <StructureSection load='2kfu' size='340' side='right' caption='[[2kfu]], [[NMR_Ensembles_of_Models | 19 NMR models]]' scene=''> | + | <StructureSection load='2kfu' size='340' side='right'caption='[[2kfu]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kfu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KFU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KFU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kfu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KFU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KFU FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 19 models</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Rv1827, MT1875, MTCY1A11.16c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=2kfu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kfu OCA], [http://pdbe.org/2kfu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kfu RCSB], [http://www.ebi.ac.uk/pdbsum/2kfu PDBsum]</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=2kfu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kfu OCA], [https://pdbe.org/2kfu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kfu RCSB], [https://www.ebi.ac.uk/pdbsum/2kfu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kfu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/GARA_MYCTU GARA_MYCTU] Involved in regulation of glutamate metabolism. Acts as a phosphorylation-dependent molecular switch that modulates the activities of Kgd, Gdh and GltB.<ref>PMID:19019160</ref> <ref>PMID:19114043</ref> <ref>PMID:19318624</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kf/2kfu_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kf/2kfu_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kfu ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Kelly, G]] | + | [[Category: Large Structures]] |
| - | [[Category: Nott, T J]]
| + | |
| - | [[Category: Smerdon, S J]]
| + | |
| - | [[Category: Fha domain]]
| + | |
| - | [[Category: Glutamate metabolism]]
| + | |
| - | [[Category: Intramolecular interaction]]
| + | |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Phosphoprotein]] | + | [[Category: Kelly G]] |
| - | [[Category: Phosphorylation]] | + | [[Category: Nott TJ]] |
| - | [[Category: Protein binding]] | + | [[Category: Smerdon SJ]] |
| Structural highlights
Function
GARA_MYCTU Involved in regulation of glutamate metabolism. Acts as a phosphorylation-dependent molecular switch that modulates the activities of Kgd, Gdh and GltB.[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
Forkhead-associated (FHA) domains have gained considerable prominence as ubiquitous phosphothreonine-dependent binding modules; however, their precise roles in serine and threonine kinase (STK) pathways and mechanisms of regulation remain unclear. From experiments with Rv1827, an FHA domain-containing protein from Mycobacterium tuberculosis, we derived a complete molecular description of an FHA-mediated STK signaling process. First, binding of the FHA domain to each of three metabolic enzyme complexes regulated their catalytic activities but did not require priming phosphorylation. However, phosphorylation of a threonine residue within a conserved amino-terminal motif of Rv1827 triggered its intramolecular association with the FHA domain of Rv1827, thus blocking its interactions with each of the three enzymes. The solution structure of this inactivated form and further mutagenic studies showed how a previously unidentified intramolecular phosphoswitch blocked the access of the target enzymes to a common FHA interaction surface and how this shared surface accommodated three functionally related, but structurally diverse, binding partners. Thus, our data reveal an unsuspected versatility in the FHA domain that allows for the transformation of multiple kinase inputs into various downstream regulatory signals.
An intramolecular switch regulates phosphoindependent FHA domain interactions in Mycobacterium tuberculosis.,Nott TJ, Kelly G, Stach L, Li J, Westcott S, Patel D, Hunt DM, Howell S, Buxton RS, O'Hare HM, Smerdon SJ Sci Signal. 2009 Mar 24;2(63):ra12. PMID:19318624[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ O'Hare HM, Duran R, Cervenansky C, Bellinzoni M, Wehenkel AM, Pritsch O, Obal G, Baumgartner J, Vialaret J, Johnsson K, Alzari PM. Regulation of glutamate metabolism by protein kinases in mycobacteria. Mol Microbiol. 2008 Dec;70(6):1408-23. doi: 10.1111/j.1365-2958.2008.06489.x., Epub 2008 Oct 17. PMID:19019160 doi:http://dx.doi.org/10.1111/j.1365-2958.2008.06489.x
- ↑ England P, Wehenkel A, Martins S, Hoos S, Andre-Leroux G, Villarino A, Alzari PM. The FHA-containing protein GarA acts as a phosphorylation-dependent molecular switch in mycobacterial signaling. FEBS Lett. 2009 Jan 22;583(2):301-7. doi: 10.1016/j.febslet.2008.12.036. Epub, 2008 Dec 27. PMID:19114043 doi:http://dx.doi.org/10.1016/j.febslet.2008.12.036
- ↑ Nott TJ, Kelly G, Stach L, Li J, Westcott S, Patel D, Hunt DM, Howell S, Buxton RS, O'Hare HM, Smerdon SJ. An intramolecular switch regulates phosphoindependent FHA domain interactions in Mycobacterium tuberculosis. Sci Signal. 2009 Mar 24;2(63):ra12. PMID:19318624 doi:2/63/ra12
- ↑ Nott TJ, Kelly G, Stach L, Li J, Westcott S, Patel D, Hunt DM, Howell S, Buxton RS, O'Hare HM, Smerdon SJ. An intramolecular switch regulates phosphoindependent FHA domain interactions in Mycobacterium tuberculosis. Sci Signal. 2009 Mar 24;2(63):ra12. PMID:19318624 doi:2/63/ra12
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