1JR1

Crystal structure of Inosine Monophosphate Dehydrogenase in complex with Mycophenolic Acid

Summary for 1JR1

• Entry DOI: 10.2210/pdb1jr1/pdb
• Related: 1AK5 1B3O 1ZFJ
• Descriptor: Inosine-5'-Monophosphate Dehydrogenase 2, POTASSIUM ION, INOSINIC ACID, ... (5 entities in total)
• Functional Keywords: dehydrogenase, impd, impdh, guanine nucleotide synthesis, mycophenolic acid, mpa, oxidoreductase
• Biological source: Cricetulus griseus (Chinese hamster)
• Cellular location: Cytoplasm : P12269
• Total number of polymer chains: 2
• Total formula weight: 113337.45

Authors

Sintchak, M.D.,Fleming, M.A.,Futer, O.,Raybuck, S.A.,Chambers, S.P.,Caron, P.R.,Murcko, M.A.,Wilson, K.P. (deposition date: 2001-08-09, release date: 2001-09-05, Last modification date: 2024-10-30)

Primary citation

Sintchak, M.D.,Fleming, M.A.,Futer, O.,Raybuck, S.A.,Chambers, S.P.,Caron, P.R.,Murcko, M.A.,Wilson, K.P.
Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid.
Cell(Cambridge,Mass.), 85:921-930, 1996

PubMed Abstract: 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.

PubMed: 8681386
DOI: 10.1016/S0092-8674(00)81275-1

Experimental method

X-RAY DIFFRACTION (2.6 Å)