3nxs

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==Crystal structure of LAO/AO transport system from Mycobacterium smegmatis bound to GDP==
==Crystal structure of LAO/AO transport system from Mycobacterium smegmatis bound to GDP==
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<StructureSection load='3nxs' size='340' side='right' caption='[[3nxs]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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<StructureSection load='3nxs' size='340' side='right'caption='[[3nxs]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[3nxs]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NXS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NXS FirstGlance]. <br>
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<table><tr><td colspan='2'>[[3nxs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NXS FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3md0|3md0]]</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MSMEG_3160 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nxs OCA], [https://pdbe.org/3nxs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nxs RCSB], [https://www.ebi.ac.uk/pdbsum/3nxs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nxs ProSAT]</span></td></tr>
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<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=3nxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nxs OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3nxs RCSB], [http://www.ebi.ac.uk/pdbsum/3nxs PDBsum]</span></td></tr>
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</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/A0QX37_MYCS2 A0QX37_MYCS2]
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nx/3nxs_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nx/3nxs_consurf.spt"</scriptWhenChecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmolCheckbox>
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</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].
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</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=3nxs ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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High-resolution three-dimensional structures of essential Mycobacterium tuberculosis (Mtb) proteins provide templates for TB drug design, but are available for only a small fraction of the Mtb proteome. Here we evaluate an intra-genus "homolog-rescue" strategy to increase the structural information available for TB drug discovery by using mycobacterial homologs with conserved active sites. Of 179 potential TB drug targets selected for x-ray structure determination, only 16 yielded a crystal structure. By adding 1675 homologs from nine other mycobacterial species to the pipeline, structures representing an additional 52 otherwise intractable targets were solved. To determine whether these homolog structures would be useful surrogates in TB drug design, we compared the active sites of 106 pairs of Mtb and non-TB mycobacterial (NTM) enzyme homologs with experimentally determined structures, using three metrics of active site similarity, including superposition of continuous pharmacophoric property distributions. Pair-wise structural comparisons revealed that 19/22 pairs with &gt;55% overall sequence identity had active site Calpha RMSD &lt;1 A, &gt;85% side chain identity, and &gt;/=80% PSAPF (similarity based on pharmacophoric properties) indicating highly conserved active site shape and chemistry. Applying these results to the 52 NTM structures described above, 41 shared &gt;55% sequence identity with the Mtb target, thus increasing the effective structural coverage of the 179 Mtb targets over three-fold (from 9% to 32%). The utility of these structures in TB drug design can be tested by designing inhibitors using the homolog structure and assaying the cognate Mtb enzyme; a promising test case, Mtb cytidylate kinase, is described. The homolog-rescue strategy evaluated here for TB is also generalizable to drug targets for other diseases.
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The methylmalonyl Co-A mutase-associated GTPase MeaB from Methylobacterium extorquens is involved in glyoxylate regulation and required for growth. In humans, mutations in the homolog methylmalonic aciduria associated protein (MMAA) cause methylmalonic aciduria, which is often fatal. The central role of MeaB from bacteria to humans suggests that MeaB is also important in other, pathogenic bacteria such as Mycobacterium tuberculosis. However, the identity of the mycobacterial MeaB homolog is presently unclear. Here, we identify the M. tuberculosis protein Rv1496 and its homologs in M. smegmatis and M. thermoresistibile as MeaB. The crystal structures of all three homologs are highly similar to MeaB and MMAA structures and reveal a characteristic three-domain homodimer with GDP bound in the G domain active site. A structure of Rv1496 obtained from a crystal grown in the presence of GTP exhibited electron density for GDP, suggesting GTPase activity. These structures identify the mycobacterial MeaB and provide a structural framework for therapeutic targeting of M. tuberculosis MeaB.
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Increasing the structural coverage of tuberculosis drug targets.,Baugh L, Phan I, Begley DW, Clifton MC, Armour B, Dranow DM, Taylor BM, Muruthi MM, Abendroth J, Fairman JW, Fox D 3rd, Dieterich SH, Staker BL, Gardberg AS, Choi R, Hewitt SN, Napuli AJ, Myers J, Barrett LK, Zhang Y, Ferrell M, Mundt E, Thompkins K, Tran N, Lyons-Abbott S, Abramov A, Sekar A, Serbzhinskiy D, Lorimer D, Buchko GW, Stacy R, Stewart LJ, Edwards TE, Van Voorhis WC, Myler PJ Tuberculosis (Edinb). 2014 Dec 19. pii: S1472-9792(14)20565-8. doi:, 10.1016/j.tube.2014.12.003. PMID:25613812<ref>PMID:25613812</ref>
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Crystal structures of Mycobacterial MeaB and MMAA-like GTPases.,Edwards TE, Baugh L, Bullen J, Baydo RO, Witte P, Thompkins K, Phan IQ, Abendroth J, Clifton MC, Sankaran B, Van Voorhis WC, Myler PJ, Staker BL, Grundner C, Lorimer DD J Struct Funct Genomics. 2015 Jun;16(2):91-9. doi: 10.1007/s10969-015-9197-2., Epub 2015 Apr 2. PMID:25832174<ref>PMID:25832174</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
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<div class="pdbe-citations 3nxs" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[ATPase|ATPase]]
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*[[ATPase 3D structures|ATPase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Mycs2]]
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[[Category: Large Structures]]
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[[Category: Structural genomic]]
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[[Category: Mycolicibacterium smegmatis MC2 155]]
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[[Category: Arginine]]
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[[Category: G-domain]]
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[[Category: Gtpase]]
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[[Category: Metallochaperone]]
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[[Category: Methylmalonic aciduria]]
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[[Category: Mislabeled as an atpase]]
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[[Category: Mycobacterium]]
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[[Category: Ornithine]]
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[[Category: Ortholog]]
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[[Category: Pathogenic bacterium]]
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[[Category: Ras-like gtpase superfamily]]
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[[Category: Ssgcid]]
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[[Category: Transport protein]]
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[[Category: Transport system]]
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[[Category: Tuberculosis]]
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Current revision

Crystal structure of LAO/AO transport system from Mycobacterium smegmatis bound to GDP

PDB ID 3nxs

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