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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=6h5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h5a OCA], [http://pdbe.org/6h5a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h5a RCSB], [http://www.ebi.ac.uk/pdbsum/6h5a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h5a 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=6h5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h5a OCA], [http://pdbe.org/6h5a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h5a RCSB], [http://www.ebi.ac.uk/pdbsum/6h5a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h5a ProSAT]</span></td></tr> | ||
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== Publication Abstract from PubMed == | |||
Tuberculosis causes over one million yearly deaths, and drug resistance is rapidly developing. Mycobacterium tuberculosis phosphatidylinositol phosphate synthase (PgsA1) is an integral membrane enzyme involved in biosynthesis of inositol-derived phospholipids required for formation of the mycobacterial cell wall, and a potential drug target. Here we present three crystal structures of M. tuberculosis PgsA1: in absence of substrates (2.9 A), in complex with Mn(2+) and citrate (1.9 A), and with the CDP-DAG substrate (1.8 A). The structures reveal atomic details of substrate binding as well as coordination and dynamics of the catalytic metal site. In addition, molecular docking supported by mutagenesis indicate a binding mode for the second substrate, D-myo-inositol-3-phosphate. Together, the data describe the structural basis for M. tuberculosis phosphatidylinositol phosphate synthesis and suggest a refined general catalytic mechanism-including a substrate-induced carboxylate shift-for Class I CDP-alcohol phosphotransferases, enzymes essential for phospholipid biosynthesis in all domains of life. | |||
Structure of Mycobacterium tuberculosis phosphatidylinositol phosphate synthase reveals mechanism of substrate binding and metal catalysis.,Grave K, Bennett MD, Hogbom M Commun Biol. 2019 May 8;2:175. doi: 10.1038/s42003-019-0427-1. eCollection 2019. PMID:31098408<ref>PMID:31098408</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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<div class="pdbe-citations 6h5a" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
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Latest revision as of 09:35, 29 May 2019
Crystal structure of Mycobacterium tuberculosis phosphatidylinositol phosphate synthase (PgsA1) in complex with manganese and citrateCrystal structure of Mycobacterium tuberculosis phosphatidylinositol phosphate synthase (PgsA1) in complex with manganese and citrate
Structural highlights
Publication Abstract from PubMedTuberculosis causes over one million yearly deaths, and drug resistance is rapidly developing. Mycobacterium tuberculosis phosphatidylinositol phosphate synthase (PgsA1) is an integral membrane enzyme involved in biosynthesis of inositol-derived phospholipids required for formation of the mycobacterial cell wall, and a potential drug target. Here we present three crystal structures of M. tuberculosis PgsA1: in absence of substrates (2.9 A), in complex with Mn(2+) and citrate (1.9 A), and with the CDP-DAG substrate (1.8 A). The structures reveal atomic details of substrate binding as well as coordination and dynamics of the catalytic metal site. In addition, molecular docking supported by mutagenesis indicate a binding mode for the second substrate, D-myo-inositol-3-phosphate. Together, the data describe the structural basis for M. tuberculosis phosphatidylinositol phosphate synthesis and suggest a refined general catalytic mechanism-including a substrate-induced carboxylate shift-for Class I CDP-alcohol phosphotransferases, enzymes essential for phospholipid biosynthesis in all domains of life. Structure of Mycobacterium tuberculosis phosphatidylinositol phosphate synthase reveals mechanism of substrate binding and metal catalysis.,Grave K, Bennett MD, Hogbom M Commun Biol. 2019 May 8;2:175. doi: 10.1038/s42003-019-0427-1. eCollection 2019. PMID:31098408[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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