1MEH
Inosine Monophosphate Dehydrogenase (IMPDH) From Tritrichomonas Foetus with IMP and MOA bound
Summary for 1MEH
| Entry DOI | 10.2210/pdb1meh/pdb |
| Related | 1AK5 1ME7 1ME8 1ME9 1MEI 1MEW |
| Descriptor | INOSINE-5'-MONOPHOSPHATE DEHYDROGENASE, POTASSIUM ION, INOSINIC ACID, ... (5 entities in total) |
| Functional Keywords | alpha beta barrel, oxidoreductase |
| Biological source | Tritrichomonas foetus |
| Total number of polymer chains | 1 |
| Total formula weight | 56263.65 |
| Authors | Prosise, G.L.,Luecke, H. (deposition date: 2002-08-08, release date: 2003-08-12, Last modification date: 2011-07-13) |
| Primary citation | Prosise, G.L.,Luecke, H. Crystal Structures of Tritrichomonas foetus Inosine Monophosphate Dehydrogenase in Complex with Substrate, Cofactor and Analogs: A Structural Basis for the Random-in Ordered-out Kinetic Mechanism J.Mol.Biol., 326:517-527, 2003 Cited by PubMed Abstract: The enzyme inosine monophosphate dehydrogenase (IMPDH) is responsible for the rate-limiting step in guanine nucleotide biosynthesis. Because it is up-regulated in rapidly proliferating cells, human type II IMPDH is actively targeted for immunosuppressive, anticancer, and antiviral chemotherapy. The enzyme employs a random-in ordered-out kinetic mechanism where substrate or cofactor can bind first but product is only released after the cofactor leaves. Due to structural and kinetic differences between mammalian and microbial enzymes, most drugs that are successful in the inhibition of mammalian IMPDH are far less effective against the microbial forms of the enzyme. It is possible that with greater knowledge of the structural mechanism of the microbial enzymes, an effective and selective inhibitor of microbial IMPDH will be developed for use as a drug against multi-drug resistant bacteria and protists. The high-resolution crystal structures of four different complexes of IMPDH from the protozoan parasite Tritrichomonas foetus have been solved: with its substrate IMP, IMP and the inhibitor mycophenolic acid (MPA), the product XMP with MPA, and XMP with the cofactor NAD(+). In addition, a potassium ion has been located at the dimer interface. A structural model for the kinetic mechanism is proposed. PubMed: 12559919DOI: 10.1016/S0022-2836(02)01383-9 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.95 Å) |
Structure validation
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