4ZQO

Crystal Structure of the Catalytic Domain of the Inosine Monophosphate Dehydrogenase from Mycobacterium tuberculosis in the complex with IMP and the inhibitor Q67

4ZQO の概要

• エントリーDOI: 10.2210/pdb4zqo/pdb
• 関連するPDBエントリー: 4ZQM 4ZQN 4ZQP 4ZQR
• 分子名称: Inosine-5'-monophosphate dehydrogenase,Inosine-5'-monophosphate dehydrogenase, INOSINIC ACID, N~2~-(2,3-dichlorophenyl)-N-[2-(pyridin-4-yl)-1,3-benzoxazol-5-yl]-L-alaninamide, ... (7 entities in total)
• 機能のキーワード: impdh, delta cbs, structural genomics, center for structural genomics of infectious diseases, csgid, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42625.40

構造登録者

Kim, Y.,Makowska-Grzyska, M.,Gu, M.,Kavitha, M.,Hedstrom, L.,Anderson, W.F.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2015-05-10, 公開日: 2015-06-17, 最終更新日: 2024-05-22)

主引用文献

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

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: 26440283
DOI: 10.1371/journal.pone.0138976

実験手法

X-RAY DIFFRACTION (1.76 Å)