Structure and catalytic mechanism of glucosamine 6-phosphate deaminase from Escherichia coli at 2.1 Å resolution
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Elsevier
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Background: Glucosamine 6-phosphate deaminase from Escherichia coli is an allosteric hexameric enzyme which catalyzes the reversible conversion of D-glucosamine 6-phosphate into D-fructose 6-phosphate and ammonium ion and is activated by N-acetyl-D-glucosamine 6-phosphate. Mechanistically, it belongs to the group of aldose-ketose isomerases, but its reaction also accomplishes a simultaneous amination/deamination. The determination of the structure of this protein provides fundamental knowledge for understanding its mode of action and the nature of allosteric conformational changes that regulate its function. Results: The crystal structure of glucosamine 6-phosphate deaminase with bound phosphate ions is presented at 2.1 Å resolution together with the refined structures of the enzyme in complexes with its allosteric activator and with a competitive inhibitor. The protein fold can be described as a modified NAD-binding domain. Conclusions: From the similarities between the three presented structures, it is concluded that these represent the enzymatically active R state conformer. A mechanism for the deaminase reaction is proposed. It comprises steps to open the pyranose ring of the substrate and a sequence of general base-catalyzed reactions to bring about isomerization and deamination, with Asp72 playing a key role as a proton exchanger.
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α/β open structure , Aldose-ketose isomerase , Allosteric enzyme , NAD-binding domain , 2 deoxy 2 aminoglucitol 6 phosphate , 2-deoxy-2-aminoglucitol-6-phosphate , bacterial protein , drug derivative , enzyme inhibitor , epimerase , fructose 6 phosphate , fructose phosphate , fructose-6-phosphate , glucosamine , glucosamine 6 phosphate , glucosamine 6 phosphate isomerase , glucosamine 6-phosphate , glucosamine-6-phosphate isomerase , glucose 6 phosphate , glucose phosphate , isomerase , nicotinamide adenine dinucleotide , phosphate , sorbitol , sugar phosphate , allosterism , binding site , biosynthesis , catalysis , chemical structure , chemistry , drug antagonism , enzymology , Escherichia coli , macromolecule , metabolism , protein conformation , X ray crystallography , Aldose-Ketose Isomerases , Allosteric Regulation , Bacterial Proteins , Binding Sites , Carbohydrate Epimerases , Catalysis , Crystallography, X-Ray , Enzyme Inhibitors , Fructosephosphates , Glucosamine , Glucose-6-Phosphate , Glucosephosphates , Macromolecular Substances , Models, Molecular , NAD , Phosphates , Protein Conformation , Sorbitol , Sugar Phosphates , Bacteria (microorganisms)
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Inglês
Citação
Structure, v. 3, n. 12, p. 1323-1332, 1995.
