Phosphatidylinositol synthesis in mycobacteria

作者: Michael Salman , John T Lonsdale , Gurdyal S Besra , Patrick J Brennan

DOI: 10.1016/S0005-2760(98)00151-9

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摘要: Abstract The metabolism and synthesis of an important mycobacterial lipid component, phosphatidylinositol (PI), its metabolites, was studied in Mycobacterium smegmatis M . subcellular fractions. Little is known about the PI prokaryotic cells. Only a cell wall fraction (P60) shown to possess synthase activity. Product identified as by migration on TLC, treatment with phospholipase C ion exchange chromatography. only major product (92.3%) when both cells P60 were labeled [ 3 H]inositol. Also, neutral inositol-containing (4.1% total label) preparations. Strangely, substrates, CDP-dipalmitoyl-DAG CDP-NBD-DAG, added assay did not stimulate H]PI NBD-PI yield At same time, addition substrates rat liver Saccharomyces cerevisiae assays resulted increase yield. Upon CHAPS assay, utilized dose-dependent manner for H]PI. These results demonstrate strict substrate specificity toward endogenous substrates. K m enzyme inositol be 25 μM; Mg 2+ stimulated greater degree than Mn Structural analogs myo -inositol, epi -inositol scyllo Zn more potent inhibitors mammalian analogs. Lack sequence homology synthases, different kinetic characteristics, existence selective physiological role mycobacteria, suggest that may good potential target anti-tuberculosis therapy.

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