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Structure of a phosphatidylinositolphosphate (PIP) synthase from Renibacterium SalmoninarumStructure of a phosphatidylinositolphosphate (PIP) synthase from Renibacterium Salmoninarum
Structural highlights
Publication Abstract from PubMedPhosphatidylinositol 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 A 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. Structural basis for phosphatidylinositol-phosphate biosynthesis.,Clarke OB, Tomasek D, Jorge CD, Dufrisne MB, Kim M, Banerjee S, Rajashankar KR, Shapiro L, Hendrickson WA, Santos H, Mancia F Nat Commun. 2015 Oct 16;6:8505. doi: 10.1038/ncomms9505. PMID:26510127[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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