6h59

Crystal structure of Mycobacterium tuberculosis phosphatidylinositol phosphate synthase (PgsA1) with CDP-DAG bound

spinqualitylabelsall models 6h59, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6h59 is a 2 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 1PE, FQT, MG, OLB, PGE, SO4 Related: 6h53 Gene: pgsA1, Rv2612c (MYCTU) Activity: CDP-diacylglycerol--inositol 3-phosphatidyltransferase, with EC number 2.7.8.11 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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