Structure and catalytic mechanism of glucosamine 6-phosphate deaminase from Escherichia coli at 2.1 Å resolution
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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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Structure, v. 3, n. 12, p. 1323-1332, 1995.
