Structure and catalytic mechanism of glucosamine 6-phosphate deaminase from Escherichia coli at 2.1 Å resolution
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1995-12-01
Autores
Oliva, Glaucius
Fontes, Marcos R.M. [UNESP]
Garratt, Richard C.
Altamirano, Myriam M.
Calcagno, Mario L.
Horjales, Eduardo
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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)
Como citar
Structure, v. 3, n. 12, p. 1323-1332, 1995.