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Biochemical characterization of the Mycobacterium tuberculosis phosphoribosyl-1-pyrophosphate synthetase

By Luke J. Alderwick, Georgina S. Lloyd, Adrian Lloyd, Andrew L. Lovering, L. Eggeling and Gurdyal S. Besra

Abstract

Mycobacterium tuberculosis arabinogalactan (AG) is an essential cell wall component. It\ud provides a molecular framework serving to connect peptidoglycan to the outer mycolic\ud acid layer. The biosynthesis of the arabinan domains of AG and lipoarabinomannan\ud (LAM), occurs via a combination of membrane bound arabinofuranosyltransferases, all\ud of which utilise decaprenol-1-monophosphorabinose as a substrate (DPA). The source of\ud arabinose ultimately destined for deposition into cell wall AG or LAM, originates\ud exclusively from phosphoribosyl-1-pyrophosphate (pRpp), a central metabolite which is\ud also required for other essential metabolic processes, such as de novo purine and\ud pyrimidne biosynthesis. In M. tuberculosis, a single pRpp synthetase enzyme (Mt-PrsA)\ud is soley responsible for the generation of pRpp, by catalysing the transfer of\ud pyrophosphate from ATP to the C1 hydroxyl position of ribose-5-phosphate. Here, we\ud report a detailed biochemical and biophysical study of Mt-PrsA, which exhibits the most\ud rapid enzyme kinetics reported for a pRpp synthetase

Topics: QR
Publisher: Oxford University Press
Year: 2011
OAI identifier: oai:wrap.warwick.ac.uk:4449

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