Crystal structure of rabbit phosphoglucose isomerase complexed with 5-phospho-D-arabinonate identifies the role of Glu357 in catalysis.

Phosphoglucose isomerase (PGI; E.C. 5.3.1.9) catalyzes the second step in glycolysis, the interconversion of D-glucose-6-phosphate and D-fructose-6-phosphate. We determined the X-ray crystal structure of rabbit PGI complexed with a competitive inhibitor of isomerase activity, 5-phospho-D-arabinonate (5PAA), at 1.9 A resolution. 5PAA is a better mimic of the proposed cis-enediol(ate) intermediate than 6-phospho-D-gluconate, which was used in a previously reported crystal structure of rabbit PGI. The orientation of 5PAA bound in the enzyme active site predicts that active site residue Glu357 is the residue that transfers a proton between C2 and C1 of the proposed cis-enediol(ate) intermediate. Amino acid residues Arg272 and Lys210 are predicted to be involved in stabilizing the negative charge of the intermediate.