5k44
From Proteopedia
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==Structure of Mycobacterium thermoresistibile trehalose-6-phosphate synthase in a complex with Trehalose-6-phosphate.== | ==Structure of Mycobacterium thermoresistibile trehalose-6-phosphate synthase in a complex with Trehalose-6-phosphate.== | ||
| - | <StructureSection load='5k44' size='340' side='right' caption='[[5k44]], [[Resolution|resolution]] 1.93Å' scene=''> | + | <StructureSection load='5k44' size='340' side='right'caption='[[5k44]], [[Resolution|resolution]] 1.93Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5k44]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K44 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5k44]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_19527 Atcc 19527]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K44 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K44 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene>, <scene name='pdbligand=T6P:TREHALOSE-6-PHOSPHATE'>T6P</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene>, <scene name='pdbligand=T6P:TREHALOSE-6-PHOSPHATE'>T6P</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RMCT_1906 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1797 ATCC 19527])</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=5k44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k44 OCA], [http://pdbe.org/5k44 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k44 RCSB], [http://www.ebi.ac.uk/pdbsum/5k44 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k44 ProSAT]</span></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=5k44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k44 OCA], [http://pdbe.org/5k44 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k44 RCSB], [http://www.ebi.ac.uk/pdbsum/5k44 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k44 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Trehalose is an essential disaccharide for mycobacteria and a key constituent of several cell wall glycolipids with fundamental roles in pathogenesis. Mycobacteria possess two pathways for trehalose biosynthesis. However, only the OtsAB pathway was found to be essential in Mycobacterium tuberculosis, with marked growth and virulence defects of OtsA mutants and strict essentiality of OtsB2. Here, we report the first mycobacterial OtsA structures from Mycobacterium thermoresistibile in both apo and ligand-bound forms. Structural information reveals three key residues in the mechanism of substrate preference that were further confirmed by site-directed mutagenesis. Additionally, we identify 2-oxoglutarate and 2-phosphoglycerate as allosteric regulators of OtsA. The structural analysis in this work strongly contributed to define the mechanisms for feedback inhibition, show different conformational states of the enzyme, and map a new allosteric site.IMPORTANCE Mycobacterial infections are a significant source of mortality worldwide, causing millions of deaths annually. Trehalose is a multipurpose disaccharide that plays a fundamental structural role in these organisms as a component of mycolic acids, a molecular hallmark of the cell envelope of mycobacteria. Here, we describe the first mycobacterial OtsA structures. We show mechanisms of substrate preference and show that OtsA is regulated allosterically by 2-oxoglutarate and 2-phosphoglycerate at an interfacial site. These results identify a new allosteric site and provide insight on the regulation of trehalose synthesis through the OtsAB pathway in mycobacteria. | ||
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| + | Mycobacterial OtsA Structures Unveil Substrate Preference Mechanism and Allosteric Regulation by 2-Oxoglutarate and 2-Phosphoglycerate.,Mendes V, Acebron-Garcia-de-Eulate M, Verma N, Blaszczyk M, Dias MVB, Blundell TL mBio. 2019 Nov 26;10(6). pii: mBio.02272-19. doi: 10.1128/mBio.02272-19. PMID:31772052<ref>PMID:31772052</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5k44" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Atcc 19527]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Blaszczyk, M]] | [[Category: Blaszczyk, M]] | ||
[[Category: Blundell, T L]] | [[Category: Blundell, T L]] | ||
Revision as of 16:29, 22 January 2020
Structure of Mycobacterium thermoresistibile trehalose-6-phosphate synthase in a complex with Trehalose-6-phosphate.
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