A mechanism of efficient G6PD inhibition by a molecular clip

Angew Chem Int Ed Engl. 2009;48(16):2886-90. doi: 10.1002/anie.200806175.

Abstract

Triple duty: A synthetic molecular clip traps nicotinamide adenine dinucleotide phosphate (NADP(+); see picture) as well as occupying both the cofactor- and the substrate-binding site in glucose-6-phosphate (G6P) dehydrogenase. This combination of two inhibition mechanisms makes the clip highly effective and selective for this enzyme over other dehydrogenases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Crystallography, X-Ray
  • Dehydroepiandrosterone / chemistry*
  • Enzyme Inhibitors / chemistry*
  • Glucosephosphate Dehydrogenase / antagonists & inhibitors*
  • Glucosephosphate Dehydrogenase / metabolism
  • Humans
  • Kinetics
  • NADP / metabolism*
  • Protein Conformation
  • Substrate Specificity
  • Thermodynamics

Substances

  • Enzyme Inhibitors
  • Dehydroepiandrosterone
  • NADP
  • Glucosephosphate Dehydrogenase