On the mechanism of the reaction catalyzed by glucose 6-phosphate dehydrogenase

Biochemistry. 1998 Mar 3;37(9):2759-67. doi: 10.1021/bi972069y.


The catalytic mechanism of glucose 6-phosphate dehydrogenase from Leuconostoc mesenteroides was investigated by replacing three amino acids, His-240, Asp-177, and His 178, with asparagine, using site-directed mutagenesis. Each of the mutant enzymes was purified to homogeneity and characterized by substrate binding studies and steady-state kinetic analyses. The three-dimensional structure of the H240N glucose 6-phosphate dehydrogenase was determined at 2.5 A resolution. The results support a mechanism in which His-240 acts as the general base that abstracts the proton from the C1-hydroxyl group of glucose 6-phosphate, and the carboxylate group of Asp-177 stabilizes the positive charge that forms on His-240 in the transition state. The results also confirm the postulated role of His-178 in binding the phosphate moiety of glucose 6-phosphate.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aspartic Acid / metabolism
  • Catalysis
  • Glucosephosphate Dehydrogenase / metabolism*
  • Histidine / metabolism
  • Leuconostoc / enzymology*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Conformation


  • Aspartic Acid
  • Histidine
  • Glucosephosphate Dehydrogenase

Associated data

  • PDB/2DPG
  • PDB/3DPG