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

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Alderwick, Luke J., Lloyd, Georgina S., Lloyd, Adrian, Lovering, Andrew L., Eggeling, L. and Besra, Gurdyal S.. (2011) Biochemical characterization of the Mycobacterium tuberculosis phosphoribosyl-1-pyrophosphate synthetase. Glycobiology, Vol.21 (No.4). pp. 410-425. ISSN 1460-2423

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Official URL: http://dx.doi.org/10.1093/glycob/cwq173

Abstract

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

Item Type: Journal Article
Subjects: Q Science > QR Microbiology
Divisions: Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Mycobacterium tuberculosis, Arabinogalactan -- Synthesis, Metabolites -- Synthesis, Ligases -- Analysis
Journal or Publication Title: Glycobiology
Publisher: Oxford University Press
ISSN: 1460-2423
Date: April 2011
Volume: Vol.21
Number: No.4
Page Range: pp. 410-425
Identification Number: 10.1093/glycob/cwq173
Status: Peer Reviewed
Access rights to Published version: Open Access
Funder: Royal Society (Great Britain), Lister Institute of Preventive Medicine, Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England)
Grant number: 081569/Z/06/Z (Wellcome)
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URI: http://wrap.warwick.ac.uk/id/eprint/4449

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