5k5c: Difference between revisions
No edit summary |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Structure of Mycobacterium thermoresistibile trehalose-6-phosphate synthase in a complex with Trehalose.== | |||
<StructureSection load='5k5c' size='340' side='right'caption='[[5k5c]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5k5c]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_thermoresistibile Mycolicibacterium thermoresistibile]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K5C FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.848Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene>, <scene name='pdbligand=PRD_900006:trehalose'>PRD_900006</scene></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=5k5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k5c OCA], [https://pdbe.org/5k5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k5c RCSB], [https://www.ebi.ac.uk/pdbsum/5k5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k5c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A117IMA6_MYCTH A0A117IMA6_MYCTH] | |||
<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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5k5c" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: Verma | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycolicibacterium thermoresistibile]] | |||
[[Category: Blaszczyk M]] | |||
[[Category: Blundell TL]] | |||
[[Category: Mendes V]] | |||
[[Category: Verma N]] | |||