The structural requirements of glucose for phosphorylation by phosphoglucomutase.

During catalysis, the phosphoryl group of phosphoglucomutase (alpha-D-glucose-1,6-bisphosphate:alpha-D-glucose-1-phosphate phosphotransferase, EC 2.7.5.1) is transferred through a nucleophilic displacement reaction to the monophosphate substrates to form the diphosphate. Some non-phosphorylated analogs of glucose have been shown to serve as effective acceptors of the active phosphate albeit at a much reduced rate. Several other analogs exhibit little or no reactivity. The relative reaction rates of the reactive analogs follow the order: thioglucose greater than alpha- or beta-D-glucose greater than D-xylose, greater than L-arabinose greater than myo-inositol. The rate of transfer increased with the increased concentration of glucose or its analogs. The products of the reaction may be acid stable ester phosphate or acid labile glycosyl phosphate as well as inorganic phosphate. S-phosphoryl (hemiacetal) thioglucose was identified as a product of the 1-thioglucose reaction. It was possible to define certain steric requirements for the orientation of the hydroxyl groups in all the reacting sugars. These requirements are limited to 3 hydroxyl groups and pertain to loci or receptors on the active site of the enzyme. These would correspond in topography to carbons 2, 3 and 4 of the glucose molecule in the enzyme substrate complex. These hydroxyl groups should be oriented equatorially and project below, above and below the plane of the pyranose ring for C-2, C-3 and C-4, respectively.