Control of isocitrate dehydrogenase activity by protein phosphorylation in Escherichia coli.

Cozzone, Alain J and El-Mansi, Mansi (2005) Control of isocitrate dehydrogenase activity by protein phosphorylation in Escherichia coli. Journal of Molecular Microbiology and Biotechnology, 9 (3-4). pp. 132-146. ISSN 1464-1801

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During aerobic growth of Escherichia coli on acetate as sole source of carbon and energy, the organism requires the operation of the glyoxylate bypass enzymes, namely isocitrate lyase (ICL) and the anaplerotic enzyme malate synthase (MS). Under these conditions, the glyoxylate bypass enzyme ICL is in direct competition with the Krebs cycle enzyme isocitrate dehydrogenase (ICDH) for their common substrate and although ICDH has a much higher affinity for isocitrate, flux of carbon through ICL is assured by virtue of high intracellular level of isocitrate and the reversible phosphorylation/inactivation of a large fraction of ICDH. Reversible inactivation is due to reversible phosphorylation catalysed by ICDH kinase/phosphatase, which harbours both catalytic activities on the same polypeptide. The catalytic activities of ICDH kinase/phosphatase constitute a moiety conserved cycle, require ATP and exhibit 'zero-order ultrasensitivity'. The structural gene encoding ICDH kinase/phosphatase (aceK) together with those encoding ICL (aceA) and MS (aceB) form an operon (aceBAK; otherwise known as the ace operon) the expression of which is intricately regulated at the transcriptional level by IclR, FadR, FruR and IHF. Although ICDH, an NADP+-dependent, non-allosteric dimer, can be phosphorylated at multiple sites, it is the phosphorylation of the Ser-113 residue that renders the enzyme catalytically inactive as it prevents isocitrate from binding to the active site, which is a consequence of the negative charge carried on phosphoserine 113 and the conformational change associated with it. The ICDH molecule readily undergo domain shifts and/or induced-fit conformational changes to accommodate the binding of ICDH kinase/phosphatase, the function of which has now been shown to be central to successful adaptation and growth of E. coli and related genera on acetate and fatty acids.

Item Type: Article
Print ISSN: 1464-1801
Electronic ISSN: 1660-2412
Uncontrolled Keywords: Escherichia coli; Acetate; Carbon flux; Glyoxylate bypass enzymes
University Divisions/Research Centres: Faculty of Health, Life & Social Sciences > School of Life Sciences
Dewey Decimal Subjects: 500 Science > 550 Earth sciences & geology
500 Science > 570 Life sciences; biology > 579 Microorganisms, fungi & algae
Library of Congress Subjects: Q Science > QR Microbiology
Item ID: 1723
Depositing User: RAE Import
Date Deposited: 15 Jul 2008 15:41
Last Modified: 26 Jul 2010 12:41

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