9JOA

PfDXR - Mn2+ - MAMK89 ternary complex

「8JNV」から置き換えられました

9JOA の概要

• エントリーDOI: 10.2210/pdb9joa/pdb
• 関連するPDBエントリー: 9JOB
• 分子名称: 1-deoxy-D-xylulose 5-phosphate reductoisomerase, apicoplastic, MANGANESE (II) ION, [(1~{S})-4-oxidanylidene-4-[oxidanyl(3-phenylpropyl)amino]-1-phenyl-butyl]phosphonic acid, ... (6 entities in total)
• 機能のキーワード: malaria, isomerase
• 由来する生物種: Plasmodium falciparum HB3
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 112828.26

構造登録者

Takada, S.,Sakamoto, Y.,Tanaka, N. (登録日: 2024-09-24, 公開日: 2025-01-01)

主引用文献

Abdullaziz, M.A.,Takada, S.,Illarionov, B.,Pessanha de Carvalho, L.,Sakamoto, Y.,Hoefmann, S.,Knak, T.,Kiffe-Delf, A.L.,Mazzone, F.,Pfeffer, K.,Kalscheuer, R.,Bacher, A.,Held, J.,Fischer, M.,Tanaka, N.,Kurz, T.
Reverse N-Substituted Hydroxamic Acid Derivatives of Fosmidomycin Target a Previously Unknown Subpocket of 1-Deoxy-d-xylulose 5-Phosphate Reductoisomerase (DXR)
ACS Infect Dis, 10:1739-1752, 2024

PubMed Abstract: Reverse analogs of the phosphonohydroxamic acid antibiotic fosmidomycin are potent inhibitors of the nonmevalonate isoprenoid biosynthesis enzyme 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR, IspC) of . Some novel analogs with large phenylalkyl substituents at the hydroxamic acid nitrogen exhibit nanomolar DXR inhibition and potent growth inhibition of parasites coupled with good parasite selectivity. X-ray crystallographic studies demonstrated that the -phenylpropyl substituent of the newly developed lead compound is accommodated in a subpocket within the DXR catalytic domain but does not reach the NADPH binding pocket of the -terminal domain. As shown for reverse carba and thia analogs, DXR selectively binds the -enantiomer of the new lead compound. In addition, some representatives of the novel inhibitor subclass are nanomolar DXR inhibitors, whereas the inhibition of DXR is considerably weaker.

PubMed: 38647213
DOI: 10.1021/acsinfecdis.4c00100

実験手法

X-RAY DIFFRACTION (1.5 Å)