6H59
Crystal structure of Mycobacterium tuberculosis phosphatidylinositol phosphate synthase (PgsA1) with CDP-DAG bound
Summary for 6H59
| Entry DOI | 10.2210/pdb6h59/pdb |
| Related | 6H53 |
| Descriptor | CDP-diacylglycerol--inositol 3-phosphatidyltransferase, MAGNESIUM ION, SULFATE ION, ... (8 entities in total) |
| Functional Keywords | phosphotransferase, glycerophospholipid metabolism, metal binding protein, membrane protein, transferase |
| Biological source | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Total number of polymer chains | 2 |
| Total formula weight | 54337.98 |
| Authors | Grave, K.,Hogbom, M. (deposition date: 2018-07-24, release date: 2019-05-15, Last modification date: 2024-01-17) |
| Primary citation | Grave, K.,Bennett, M.D.,Hogbom, M. Structure ofMycobacterium tuberculosisphosphatidylinositol phosphate synthase reveals mechanism of substrate binding and metal catalysis. Commun Biol, 2:175-175, 2019 Cited by PubMed Abstract: Tuberculosis causes over one million yearly deaths, and drug resistance is rapidly developing. 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 PgsA1: in absence of substrates (2.9 Å), in complex with Mn and citrate (1.9 Å), and with the CDP-DAG substrate (1.8 Å). 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--inositol-3-phosphate. Together, the data describe the structural basis for 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. PubMed: 31098408DOI: 10.1038/s42003-019-0427-1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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