3WQS

Crystal structure of pfdxr complexed with inhibitor-126

3WQS の概要

• エントリーDOI: 10.2210/pdb3wqs/pdb
• 関連するPDBエントリー: 3WQQ 3WQR
• 分子名称: 1-deoxy-D-xylulose 5-phosphate reductoisomerase, apicoplast, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: reductoisomerase, 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: 1
• 化学式量合計: 56904.56

構造登録者

Tanaka, N.,Umeda, T. (登録日: 2014-01-31, 公開日: 2014-11-26, 最終更新日: 2024-03-20)

主引用文献

Konzuch, S.,Umeda, T.,Held, J.,Hahn, S.,Brucher, K.,Lienau, C.,Behrendt, C.T.,Grawert, T.,Bacher, A.,Illarionov, B.,Fischer, M.,Mordmuller, B.,Tanaka, N.,Kurz, T.
Binding Modes of Reverse Fosmidomycin Analogs toward the Antimalarial Target IspC.
J.Med.Chem., 57:8827-8838, 2014

PubMed Abstract: 1-Deoxy-d-xylulose 5-phosphate reductoisomerase of Plasmodium falciparum (PfIspC, PfDxr), believed to be the rate-limiting enzyme of the nonmevalonate pathway of isoprenoid biosynthesis (MEP pathway), is a clinically validated antimalarial target. The enzyme is efficiently inhibited by the natural product fosmidomycin. To gain new insights into the structure activity relationships of reverse fosmidomycin analogs, several reverse analogs of fosmidomycin were synthesized and biologically evaluated. The 4-methoxyphenyl substituted derivative 2c showed potent inhibition of PfIspC as well as of P. falciparum growth and was more than one order of magnitude more active than fosmidomycin. The binding modes of three new derivatives in complex with PfIspC, reduced nicotinamide adenine dinucleotide phosphate, and Mg(2+) were determined by X-ray structure analysis. Notably, PfIspC selectively binds the S-enantiomers of the study compounds.

PubMed: 25254502
DOI: 10.1021/jm500850y

実験手法

X-RAY DIFFRACTION (2.35 Å)