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The structure of CodY, a GTP and isoleucine responsive regulator of stationary phase and virulence in Gram-positive bacteria

Levdikov, V.M., Blagova, E., Joseph, P., Sonenshein, A.L. and Wilkinson, A.J. (2006) The structure of CodY, a GTP and isoleucine responsive regulator of stationary phase and virulence in Gram-positive bacteria. Journal of Biological Chemistry, 281 (16). pp. 11366-11373. ISSN 0021-9258

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CodY is a global regulator of transcription in Gram-positive bacteria. It represses during growth genes required for adaptation to nutrient limitation, including virulence genes in some human pathogens. CodY activity is regulated by GTP and branched chain amino acids, metabolites whose intracellular concentrations drop as cells enter stationary phase. Although CodY has a highly conserved sequence, it has no significant similarity to proteins of known structure. Here we report crystal structures of two fragments of CodY from Bacillus subtilis that clearly constitute its cofactor and DNA binding domains and reveal that CodY is a chimera of previously observed folding units. The N-terminal cofactor-binding fragment adopts a fold reminiscent of the GAF domains found in cyclic nucleotide phosphodiesterases and adenylate cyclases. It is a dimer stabilized by an intermolecular six -helical bundle that buries an extensive apolar surface rich in residues invariant in CodY orthologues. The branched chain amino acid ligands reside in hydrophobic pockets of each monomer distal to the dimer-forming surface. The structure of the C-terminal DNA binding domain belongs to the winged helix-turn-helix family. The implications of the structure for DNA binding by CodY and its control by cofactor binding are discussed.

Item Type: Article
Institution: The University of York
Academic Units: The University of York > Chemistry (York)
Depositing User: York RAE Import
Date Deposited: 23 Apr 2009 11:19
Last Modified: 23 Apr 2009 11:19
Published Version: http://dx.doi.org/10.1074/jbc.M513015200
Status: Published
Publisher: The American Society for Biochemistry and Molecular Biology
Identification Number: 10.1074/jbc.M513015200
URI: http://eprints.whiterose.ac.uk/id/eprint/6577

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