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Molecular Basis of Phosphatidyl-myo-inositol Mannoside Biosynthesis and Regulation in Mycobacteria
Authors:Marcelo E Guerin  Jana Korduláková  Pedro M Alzari  Patrick J Brennan  Mary Jackson
Abstract:Phosphatidyl-myo-inositol mannosides (PIMs) are unique glycolipids found in abundant quantities in the inner and outer membranes of the cell envelope of all Mycobacterium species. They are based on a phosphatidyl-myo-inositol lipid anchor carrying one to six mannose residues and up to four acyl chains. PIMs are considered not only essential structural components of the cell envelope but also the structural basis of the lipoglycans (lipomannan and lipoarabinomannan), all important molecules implicated in host-pathogen interactions in the course of tuberculosis and leprosy. Although the chemical structure of PIMs is now well established, knowledge of the enzymes and sequential events leading to their biosynthesis and regulation is still incomplete. Recent advances in the identification of key proteins involved in PIM biogenesis and the determination of the three-dimensional structures of the essential phosphatidyl-myo-inositol mannosyltransferase PimA and the lipoprotein LpqW have led to important insights into the molecular basis of this pathway.
Keywords:Bacterial Metabolism  Cell Wall  Glycerophospholipid  Lipid Synthesis  Membrane Enzymes  Mycobacterium  Glycosyltransferase  Phosphatidylinositol Mannosides  Tuberculosis
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