4KP7

Structure of Plasmodium IspC in complex with a beta-thia-isostere derivative of Fosmidomycin

4KP7 の概要

• エントリーDOI: 10.2210/pdb4kp7/pdb
• 関連するPDBエントリー: 3AU8 3AU9
• 分子名称: 1-deoxy-D-xylulose 5-phosphate reductoisomerase, apicoplast, MANGANESE (III) ION, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, ... (5 entities in total)
• 機能のキーワード: dxp pathway, drug optimization, non-covalent inhibition, malaria, tuberculosis, rossmann fold, reductoisomerase, nadph binding, apicoplast, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• 由来する生物種: Plasmodium falciparum
• 細胞内の位置: Plastid, apicoplast: O96693
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 98739.81

構造登録者

Kunfermann, A.,Bacher, A.,Groll, M. (登録日: 2013-05-13, 公開日: 2013-10-02, 最終更新日: 2023-09-20)

主引用文献

Kunfermann, A.,Lienau, C.,Illarionov, B.,Held, J.,Grawert, T.,Behrendt, C.T.,Werner, P.,Hahn, S.,Eisenreich, W.,Riederer, U.,Mordmuller, B.,Bacher, A.,Fischer, M.,Groll, M.,Kurz, T.
IspC as Target for Antiinfective Drug Discovery: Synthesis, Enantiomeric Separation, and Structural Biology of Fosmidomycin Thia Isosters.
J.Med.Chem., 56:8151-8162, 2013

PubMed Abstract: The emergence and spread of multidrug-resistant pathogens are widely believed to endanger human health. New drug targets and lead compounds exempt from cross-resistance with existing drugs are urgently needed. We report on the synthesis and properties of "reverse" thia analogs of fosmidomycin, which inhibit the first committed enzyme of a metabolic pathway that is essential for the causative agents of tuberculosis and malaria but is absent in the human host. Notably, IspC displays a high level of enantioselectivity for an α-substituted fosmidomycin derivative.

PubMed: 24032981
DOI: 10.1021/jm4012559

実験手法

X-RAY DIFFRACTION (2 Å)