2gej
From Proteopedia
Crystal Structure of phosphatidylinositol mannosyltransferase (PimA) from Mycobacterium smegmatis in complex with GDP-Man
Structural highlights
Function[PIMA_MYCS2] Catalyzes the addition of a mannose residue from GDP-D-mannose to the position 2 of a phosphatidyl-myo-inositol (PI) to generate a phosphatidyl-myo-inositol bearing an alpha-1,2-linked mannose residue (PIM1). Contrary to PimB, the mannosyltransferase PimA is unable to transfer a mannose residue to the position 6 of the phosphatidyl-myo-inositola of PIM1.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMycobacterial phosphatidylinositol mannosides (PIMs) and metabolically derived cell wall lipoglycans play important roles in host-pathogen interactions, but their biosynthetic pathways are poorly understood. Here we focus on Mycobacterium smegmatis PimA, an essential enzyme responsible for the initial mannosylation of phosphatidylinositol. The structure of PimA in complex with GDP-mannose shows the two-domain organization and the catalytic machinery typical of GT-B glycosyltransferases. PimA is an amphitrophic enzyme that binds mono-disperse phosphatidylinositol, but its transferase activity is stimulated by high concentrations of non-substrate anionic surfactants, indicating that the early stages of PIM biosynthesis involve lipid-water interfacial catalysis. Based on structural, calorimetric, and mutagenesis studies, we propose a model wherein PimA attaches to the membrane through its N-terminal domain, and this association leads to enzyme activation. Our results reveal a novel mode of phosphatidylinositol recognition and provide a template for the development of potential antimycobacterial compounds. Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria.,Guerin ME, Kordulakova J, Schaeffer F, Svetlikova Z, Buschiazzo A, Giganti D, Gicquel B, Mikusova K, Jackson M, Alzari PM J Biol Chem. 2007 Jul 13;282(28):20705-14. Epub 2007 May 16. PMID:17510062[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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