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5oce
From Proteopedia
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(New page: '''Unreleased structure''' The entry 5oce is ON HOLD Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==THE MOLECULAR MECHANISM OF SUBSTRATE RECOGNITION AND CATALYSIS OF THE MEMBRANE ACYLTRANSFERASE PatA -- Complex of PatA with palmitate, mannose, and palmitoyl-6-mannose== | |
| + | <StructureSection load='5oce' size='340' side='right'caption='[[5oce]], [[Resolution|resolution]] 2.41Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5oce]] is a 4 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=5OCE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OCE 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]] 2.41Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9R2:[(2~{R},3~{S},4~{S},5~{S},6~{S})-3,4,5,6-tetrakis(oxidanyl)oxan-2-yl]methyl+hexadecanoate'>9R2</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</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=5oce FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oce OCA], [https://pdbe.org/5oce PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oce RCSB], [https://www.ebi.ac.uk/pdbsum/5oce PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oce ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ACYLT_MYCS2 ACYLT_MYCS2] Catalyzes the acylation to the position 6 of the alpha-1,2-linked mannose residue of the phosphatidyl-myo-inositol dimannoside (PIM2) or monomannoside (PIM1).<ref>PMID:12851411</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Glycolipids play a central role in a variety of important biological processes in all living organisms. PatA is a membrane acyltransferase involved in the biosynthesis of phosphatidyl-myo-inositol mannosides (PIMs), key structural elements, and virulence factors of Mycobacterium tuberculosis. PatA catalyzes the transfer of a palmitoyl moiety from palmitoyl-CoA to the 6-position of the mannose ring linked to the 2-position of inositol in PIM1/PIM2. We report here the crystal structure of PatA in the presence of 6-O-palmitoyl-alpha-d-mannopyranoside, unraveling the acceptor binding mechanism. The acceptor mannose ring localizes in a cavity at the end of a surface-exposed long groove where the active site is located, whereas the palmitate moiety accommodates into a hydrophobic pocket deeply buried in the alpha/beta core of the protein. Both fatty acyl chains of the PIM2 acceptor are essential for the reaction to take place, highlighting their critical role in the generation of a competent active site. By the use of combined structural and quantum-mechanics/molecular-mechanics (QM/MM) metadynamics, we unravel the catalytic mechanism of PatA at the atomic-electronic level. Our study provides a detailed structural rationale for a stepwise reaction, with the generation of a tetrahedral transition state for the rate-determining step. Finally, the crystal structure of PatA in the presence of beta-d-mannopyranose and palmitate suggests an inhibitory mechanism for the enzyme, providing exciting possibilities for inhibitor design and the discovery of chemotherapeutic agents against this major human pathogen. | ||
| - | + | The Molecular Mechanism of Substrate Recognition and Catalysis of the Membrane Acyltransferase PatA from Mycobacteria.,Tersa M, Raich L, Albesa-Jove D, Trastoy B, Prandi J, Gilleron M, Rovira C, Guerin ME ACS Chem Biol. 2017 Dec 11. doi: 10.1021/acschembio.7b00578. PMID:29185694<ref>PMID:29185694</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5oce" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mycolicibacterium smegmatis MC2 155]] | ||
| + | [[Category: Albesa-Jove D]] | ||
| + | [[Category: Guerin ME]] | ||
| + | [[Category: Tersa M]] | ||
Current revision
THE MOLECULAR MECHANISM OF SUBSTRATE RECOGNITION AND CATALYSIS OF THE MEMBRANE ACYLTRANSFERASE PatA -- Complex of PatA with palmitate, mannose, and palmitoyl-6-mannose
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