Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid

Cell. 1996 Jun 14;85(6):921-30. doi: 10.1016/s0092-8674(00)81275-1.


The structure of inosine-5'-monophosphate dehydrogenase (IMPDH) in complex with IMP and mycophenolic acid (MPA) has been determined by X-ray diffraction. IMPDH plays a central role in B and T lymphocyte replication. MPA is a potent IMPDH inhibitor and the active metabolite of an immunosuppressive drug recently approved for the treatment of allograft rejection. IMPDH comprises two domains: a core domain, which is an alpha/beta barrel and contains the active site, and a flanking domain. The complex, in combination with mutagenesis and kinetic data, provides a structural basis for understanding the mechanism of IMPDH activity and indicates that MPA inhibits IMPDH by acting as a replacement for the nicotinamide portion of the nicotinamide adenine dinucleotide cofactor and a catalytic water molecule.

MeSH terms

  • Animals
  • Binding Sites
  • Cricetinae
  • Cricetulus
  • Crystallography, X-Ray
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors
  • IMP Dehydrogenase / chemistry*
  • IMP Dehydrogenase / genetics
  • IMP Dehydrogenase / metabolism*
  • Immunosuppressive Agents / metabolism*
  • Inosine Monophosphate / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Mycophenolic Acid / analogs & derivatives
  • Mycophenolic Acid / metabolism*
  • Potassium / metabolism
  • Protein Binding
  • Protein Conformation
  • Structure-Activity Relationship


  • Immunosuppressive Agents
  • Inosine Monophosphate
  • IMP Dehydrogenase
  • Mycophenolic Acid
  • Potassium

Associated data

  • GENBANK/U13372