5D92

Structure of a phosphatidylinositolphosphate (PIP) synthase from Renibacterium Salmoninarum

Summary for 5D92

• Entry DOI: 10.2210/pdb5d92/pdb
• Related: 5D91
• Descriptor: AF2299 protein,Phosphatidylinositol synthase, Octadecane, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: membrane protein, enzyme, lipid biosynthesis, phosphatidylinositol
• Biological source: Archaeoglobus fulgidus; More
• Total number of polymer chains: 4
• Total formula weight: 163008.66

Authors

Clarke, O.B.,Tomasek, D.T.,Jorge, C.D.,Belcher Dufrisne, M.,Kim, M.,Banerjee, S.,Rajashankar, K.R.,Hendrickson, W.A.,Santos, H.,Mancia, F. (deposition date: 2015-08-18, release date: 2015-11-04, Last modification date: 2023-09-27)

Primary citation

Clarke, O.B.,Tomasek, D.,Jorge, C.D.,Dufrisne, M.B.,Kim, M.,Banerjee, S.,Rajashankar, K.R.,Shapiro, L.,Hendrickson, W.A.,Santos, H.,Mancia, F.
Structural basis for phosphatidylinositol-phosphate biosynthesis.
Nat Commun, 6:8505-8505, 2015

PubMed Abstract: Phosphatidylinositol is critical for intracellular signalling and anchoring of carbohydrates and proteins to outer cellular membranes. The defining step in phosphatidylinositol biosynthesis is catalysed by CDP-alcohol phosphotransferases, transmembrane enzymes that use CDP-diacylglycerol as donor substrate for this reaction, and either inositol in eukaryotes or inositol phosphate in prokaryotes as the acceptor alcohol. Here we report the structures of a related enzyme, the phosphatidylinositol-phosphate synthase from Renibacterium salmoninarum, with and without bound CDP-diacylglycerol to 3.6 and 2.5 Å resolution, respectively. These structures reveal the location of the acceptor site, and the molecular determinants of substrate specificity and catalysis. Functional characterization of the 40%-identical ortholog from Mycobacterium tuberculosis, a potential target for the development of novel anti-tuberculosis drugs, supports the proposed mechanism of substrate binding and catalysis. This work therefore provides a structural and functional framework to understand the mechanism of phosphatidylinositol-phosphate biosynthesis.

PubMed: 26510127
DOI: 10.1038/ncomms9505

Experimental method

X-RAY DIFFRACTION (3.62 Å)