6WM5

Structure of a phosphatidylinositol-phosphate synthase (PIPS) from Mycobacterium kansasii

Summary for 6WM5

• Entry DOI: 10.2210/pdb6wm5/pdb
• Descriptor: AfCTD-Phosphatidylinositol-phosphate synthase (PIPS) fusion, CITRATE ANION, SODIUM ION, ... (10 entities in total)
• Functional Keywords: cdp-alcohol phosphotransferase, structural genomics, psi-biology, new york consortium on membrane protein structure, nycomps, membrane protein
• Biological source: Archaeoglobus fulgidus; More
• Total number of polymer chains: 2
• Total formula weight: 91766.40

Authors

Belcher Dufrisne, M.,Jorge, C.D.,Timoteo, C.G.,Petrou, V.I.,Ashraf, K.U.,Banerjee, S.,Clarke, O.B.,Santos, H.,Mancia, F.,New York Consortium on Membrane Protein Structure (NYCOMPS) (deposition date: 2020-04-20, release date: 2020-05-27, Last modification date: 2023-10-18)

Primary citation

Belcher Dufrisne, M.,Jorge, C.D.,Timoteo, C.G.,Petrou, V.I.,Ashraf, K.U.,Banerjee, S.,Clarke, O.B.,Santos, H.,Mancia, F.
Structural and Functional Characterization of Phosphatidylinositol-Phosphate Biosynthesis in Mycobacteria.
J.Mol.Biol., 432:5137-5151, 2020

PubMed Abstract: In mycobacteria, phosphatidylinositol (PI) acts as a common lipid anchor for key components of the cell wall, including the glycolipids phosphatidylinositol mannoside, lipomannan, and lipoarabinomannan. 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 cytidine diphosphate-diacylglycerol and inositol-phosphate to yield phosphatidylinositol-phosphate, the immediate precursor to PI. This reaction is catalyzed by the cytidine diphosphate-alcohol phosphotransferase phosphatidylinositol-phosphate synthase (PIPS), an essential enzyme for mycobacterial viability. Here we present structures of PIPS from Mycobacterium kansasii with and without evidence of donor and acceptor substrate binding obtained using a crystal engineering approach. PIPS from Mycobacterium kansasii is 86% identical to the ortholog from M. 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.

PubMed: 32389689
DOI: 10.1016/j.jmb.2020.04.028

Experimental method

X-RAY DIFFRACTION (1.961 Å)