4ZQR
Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis
Summary for 4ZQR
| Entry DOI | 10.2210/pdb4zqr/pdb |
| Related | 4ZQM 4ZQN 4ZQO 4ZQP |
| Descriptor | Inosine-5'-monophosphate dehydrogenase,Inosine-5'-monophosphate dehydrogenase, PHOSPHATE ION, S-1,2-PROPANEDIOL, ... (6 entities in total) |
| Functional Keywords | impdh, delta cbs, structural genomics, center for structural genomics of infectious diseases, csgid, oxidoreductase |
| Biological source | Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) |
| Total number of polymer chains | 4 |
| Total formula weight | 169261.20 |
| Authors | Kim, Y.,Makowska-Grzyska, M.,Gu, M.,Kavitha, M.,Hedstrom, L.,Anderson, W.F.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2015-05-11, release date: 2015-06-17, Last modification date: 2024-05-22) |
| Primary citation | Makowska-Grzyska, M.,Kim, Y.,Gorla, S.K.,Wei, Y.,Mandapati, K.,Zhang, M.,Maltseva, N.,Modi, G.,Boshoff, H.I.,Gu, M.,Aldrich, C.,Cuny, G.D.,Hedstrom, L.,Joachimiak, A. Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds. Plos One, 10:e0138976-e0138976, 2015 Cited by PubMed Abstract: Tuberculosis (TB) remains a worldwide problem and the need for new drugs is increasingly more urgent with the emergence of multidrug- and extensively-drug resistant TB. Inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) from Mycobacterium tuberculosis (Mtb) is an attractive drug target. The enzyme catalyzes the conversion of inosine 5'-monophosphate into xanthosine 5'-monophosphate with the concomitant reduction of NAD+ to NADH. This reaction controls flux into the guanine nucleotide pool. We report seventeen selective IMPDH inhibitors with antitubercular activity. The crystal structures of a deletion mutant of MtbIMPDH2 in the apo form and in complex with the product XMP and substrate NAD+ are determined. We also report the structures of complexes with IMP and three structurally distinct inhibitors, including two with antitubercular activity. These structures will greatly facilitate the development of MtbIMPDH2-targeted antibiotics. PubMed: 26440283DOI: 10.1371/journal.pone.0138976 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.692 Å) |
Structure validation
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