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Crystal and solution studies reveal that the transcriptional regulator AcnR of Corynebacterium glutamicum is regulated by citrate-Mg binding to a non-canonical pocket

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JournalThe Journal of biological chemistry
DatePublished - 31 May 2013
Issue number22
Volume288
Number of pages13
Pages (from-to)15800-15812
Original languageEnglish

Abstract

Corynebacterium glutamicum is an important industrial bacterium as well as a model organism for the order Corynebacteriales, whose citric acid cycle occupies a central position in energy and precursor supply. Expression of aconitase, which isomerizes citrate into isocitrate, is controlled by several transcriptional regulators, including the dimeric aconitase repressor AcnR, assigned by sequence identity to the TetR family. We report the structures of AcnR in two crystal forms together with ligand binding experiments and in vivo studies. First, there is a citrate-Mg moiety bound in both forms, not in the canonical TetR ligand binding site but rather in a second pocket more distant from the DNA binding domain. Second, the citrate-Mg binds with a K of 6 mM, within the range of physiological significance. Third, citrate-Mg lowers the affinity of AcnR for its target DNA in vitro. Fourth, analyses of several AcnR point mutations provide evidence for the possible involvement of the corresponding residues in ligand binding,DNA binding, and signal transfer. AcnR derivatives defective in citrate-Mg binding severely inhibit growth of C. glutamicum on citrate. Finally, the structures do have a pocket corresponding to the canonical tetracycline site, and although we have not identified a ligand that binds there, comparison of the two crystal forms suggests differences in the region of the canonical pocket that may indicate a biological significance.

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