Novel catalytic mechanism of glycoside hydrolysis based on the structure of an NAD+/Mn2+ -dependent phospho-alpha-glucosidase from Bacillus subtilis.

GlvA, a 6-phospho-alpha-glucosidase from Bacillus subtilis, catalyzes the hydrolysis of maltose-6'-phosphate and belongs to glycoside hydrolase family GH4. GH4 enzymes are unique in their requirement for NAD(H) and a divalent metal for activity. We have determined the crystal structure of GlvA in complex with its ligands to 2.05 A resolution. Analyses of the active site architecture, in conjunction with mechanistic studies and precedent from the nucleotide diphosphate hexose dehydratases and other systems, suggest a novel mechanism of glycoside hydrolysis by GlvA that involves both the NAD(H) and the metal.

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