High-resolution structure of an atypical alpha-phosphoglucomutase related to eukaryotic phosphomannomutases

The first structure of a bacterial alpha-phosphoglucomutase with an overall fold similar to eukaryotic phosphomannomutases is reported. Unlike most alpha-phosphoglucomutases within the alpha-D-phosphohexomutase superfamily, it belongs to subclass IIb of the haloacid dehalogenase superfamily (HADSF). It catalyzes the reversible conversion of alpha-glucose 1-phosphate to glucose 6-phosphate. The crystal structure of alpha-phosphoglucomutase from Lactococcus lactis (APGM) was determined at 1.5 angstrom resolution and contains a sulfate and a glycerol bound at the enzyme active site that partially mimic the substrate. A dimeric form of APGM is present in the crystal and in solution, an arrangement that may be functionally relevant. The catalytic mechanism of APGM and its strict specificity towards alpha-glucose 1-phosphate are discussed.