6wmv
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==Structure of a phosphatidylinositol-phosphate synthase (PIPS) from Mycobacterium kansasii with evidence of substrate binding== | ==Structure of a phosphatidylinositol-phosphate synthase (PIPS) from Mycobacterium kansasii with evidence of substrate binding== | ||
| - | <StructureSection load='6wmv' size='340' side='right'caption='[[6wmv]]' scene=''> | + | <StructureSection load='6wmv' size='340' side='right'caption='[[6wmv]], [[Resolution|resolution]] 2.14Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WMV OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6wmv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus] and [https://en.wikipedia.org/wiki/Mycobacterium_kansasii_ATCC_12478 Mycobacterium kansasii ATCC 12478]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WMV FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.142Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=8K6:OCTADECANE'>8K6</scene>, <scene name='pdbligand=C5P:CYTIDINE-5-MONOPHOSPHATE'>C5P</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LIP:L-MYO-INOSITOL-1-PHOSPHATE'>LIP</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=TCE:3,3,3-PHOSPHANETRIYLTRIPROPANOIC+ACID'>TCE</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=6wmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wmv OCA], [https://pdbe.org/6wmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wmv RCSB], [https://www.ebi.ac.uk/pdbsum/6wmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wmv ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/O27985_ARCFU O27985_ARCFU] [https://www.uniprot.org/uniprot/U5WZP7_MYCKA U5WZP7_MYCKA] Catalyzes the conjugation of the 1'-hydroxyl group of D-myo-inositol-3-phosphate (also named L-myo-inositol-1-phosphate) with a lipid tail of cytidine diphosphate diacylglycerol (CDP-DAG), forming phosphatidylinositol phosphate (PIP) and CMP. PIP is a precursor of phosphatidylinositol (PI) which is an essential lipid required for cell wall formation.[HAMAP-Rule:MF_02241] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In mycobacteria, phosphatidylinositol (PI) acts as a common lipid anchor for key components of the cell wall, including the glycolipids phosphatidylinositol mannoside (PIM), lipomannan (LM) and lipoarabinomannan (LAM). Glycolipids in Mycobacterium tuberculosis, the causative agent of tuberculosis, are important virulence factors that modulate the host immune response. The identity-defining step in PI biosynthesis in prokaryotes, unique to mycobacteria and few other bacterial species, is the reaction between CDP-diacylglycerol and inositol-phosphate to yield phosphatidylinositol-phosphate, the immediate precursor to PI. This reaction is catalyzed by the CDP-alcohol phosphotransferase phosphatidylinositol-phosphate synthase (PIPS), an essential enzyme for mycobacterial viability. Here we present structures of PIPS from Mycobacterium kansasii (MkPIPS) with and without evidence of donor and acceptor substrate binding obtained using a crystal engineering approach. MkPIPS is 86% identical to the ortholog from Mycobacterium tuberculosis and catalytically active. Functional experiments guided by our structural results allowed us to further characterize the molecular determinants of substrate specificity and catalysis in a new mycobacterial species. This work provides a framework to strengthen our understanding of phosphatidylinositol-phosphate biosynthesis in the context of mycobacterial pathogens. | ||
| + | |||
| + | Structural and Functional Characterization of Phosphatidylinositol-Phosphate Biosynthesis in Mycobacteria.,Belcher Dufrisne M, Jorge CD, Timoteo CG, Petrou VI, Ashraf KU, Banerjee S, Clarke OB, Santos H, Mancia F J Mol Biol. 2020 May 7. pii: S0022-2836(20)30330-2. doi:, 10.1016/j.jmb.2020.04.028. PMID:32389689<ref>PMID:32389689</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6wmv" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Archaeoglobus fulgidus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium kansasii ATCC 12478]] | ||
[[Category: Ashraf KU]] | [[Category: Ashraf KU]] | ||
[[Category: Banerjee S]] | [[Category: Banerjee S]] | ||
Current revision
Structure of a phosphatidylinositol-phosphate synthase (PIPS) from Mycobacterium kansasii with evidence of substrate binding
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