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|2dgk, resolution 1.90Å ()|
|Gene:||gadB (Escherichia coli)|
|Related:||1pmm, 1pmo, 2dgl, 2dgm|
Crystal structure of an N-terminal deletion mutant of Escherichia coli GadB in an autoinhibited state (aldamine)
Escherichia coli and other enterobacteria exploit the H+ -consuming reaction catalysed by glutamate decarboxylase to survive the stomach acidity before reaching the intestine. Here we show that chloride, extremely abundant in gastric secretions, is an allosteric activator producing a 10-fold increase in the decarboxylase activity at pH 5.6. Cooperativity and sensitivity to chloride were lost when the N-terminal 14 residues, involved in the formation of two triple-helix bundles, were deleted by mutagenesis. X-ray structures, obtained in the presence of the substrate analogue acetate, identified halide-binding sites at the base of each N-terminal helix, showed how halide binding is responsible for bundle stability and demonstrated that the interconversion between active and inactive forms of the enzyme is a stepwise process. We also discovered an entirely novel structure of the cofactor pyridoxal 5'-phosphate (aldamine) to be responsible for the reversibly inactivated enzyme. Our results link the entry of chloride ions, via the H+/Cl- exchange activities of ClC-ec1, to the trigger of the acid stress response in the cell when the intracellular proton concentration has not yet reached fatal values.
Escherichia coli acid resistance: pH-sensing, activation by chloride and autoinhibition in GadB., Gut H, Pennacchietti E, John RA, Bossa F, Capitani G, De Biase D, Grutter MG, EMBO J. 2006 Jun 7;25(11):2643-51. Epub 2006 May 4. PMID:16675957
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
- Gut H, Pennacchietti E, John RA, Bossa F, Capitani G, De Biase D, Grutter MG. Escherichia coli acid resistance: pH-sensing, activation by chloride and autoinhibition in GadB. EMBO J. 2006 Jun 7;25(11):2643-51. Epub 2006 May 4. PMID:16675957
- Capitani G, De Biase D, Aurizi C, Gut H, Bossa F, Grutter MG. Crystal structure and functional analysis of Escherichia coli glutamate decarboxylase. EMBO J. 2003 Aug 15;22(16):4027-37. PMID:12912902 doi:http://dx.doi.org/10.1093/emboj/cdg403