6H53

Crystal structure of Mycobacterium tuberculosis phosphatidylinositol phosphate synthase (PgsA1) in apo form

6H53 の概要

• エントリーDOI: 10.2210/pdb6h53/pdb
• 分子名称: CDP-diacylglycerol--inositol 3-phosphatidyltransferase, SULFATE ION, UNKNOWN BRANCHED FRAGMENT OF PHOSPHOLIPID (3 entities in total)
• 機能のキーワード: phosphotransferase glycerophospholipid metabolism metal binding protein, transferase
• 由来する生物種: Mycobacterium tuberculosis H37Rv
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 49710.72

構造登録者

Grave, K.,Hogbom, M. (登録日: 2018-07-23, 公開日: 2019-05-15, 最終更新日: 2024-01-17)

主引用文献

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

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: 31098408
DOI: 10.1038/s42003-019-0427-1

実験手法

X-RAY DIFFRACTION (2.9 Å)