1NHW

Crystal Structure Analysis of Plasmodium falciparum enoyl-acyl-carrier-protein reductase

1NHW の概要

• エントリーDOI: 10.2210/pdb1nhw/pdb
• 関連するPDBエントリー: 1NHD 1NHG
• 分子名称: enoyl-acyl carrier reductase, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, 2-(2,4-DICHLORO-PHENYLAMINO)-PHENOL, ... (4 entities in total)
• 機能のキーワード: rossmann fold, short chain dehydrogenase reductase, nadh, oxidoreductase
• 由来する生物種: Plasmodium falciparum (malaria parasite P. falciparum); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 66983.57

構造登録者

Perozzo, R.,Kuo, M.,Sidhu, A.S.,Valiyaveettil, J.T.,Bittman, R.,Jacobs Jr., W.R.,Fidock, D.A.,Sacchettini, J.C. (登録日: 2002-12-19, 公開日: 2003-02-25, 最終更新日: 2024-02-14)

主引用文献

Perozzo, R.,Kuo, M.,Sidhu, A.S.,Valiyaveettil, J.T.,Bittman, R.,Jacobs Jr., W.R.,Fidock, D.A.,Sacchettini, J.C.
Structural Elucidation of the Specificity of the Antibacterial Agent Triclosan for Malarial Enoyl Acyl Carrier Protein Reductase Year
J.Biol.Chem., 277:13106-13114, 2002

PubMed Abstract: The human malaria parasite Plasmodium falciparum synthesizes fatty acids using a type II pathway that is absent in humans. The final step in fatty acid elongation is catalyzed by enoyl acyl carrier protein reductase, a validated antimicrobial drug target. Here, we report the cloning and expression of the P. falciparum enoyl acyl carrier protein reductase gene, which encodes a 50-kDa protein (PfENR) predicted to target to the unique parasite apicoplast. Purified PfENR was crystallized, and its structure resolved as a binary complex with NADH, a ternary complex with triclosan and NAD(+), and as ternary complexes bound to the triclosan analogs 1 and 2 with NADH. Novel structural features were identified in the PfENR binding loop region that most closely resembled bacterial homologs; elsewhere the protein was similar to ENR from the plant Brassica napus (root mean square for Calphas, 0.30 A). Triclosan and its analogs 1 and 2 killed multidrug-resistant strains of intra-erythrocytic P. falciparum parasites at sub to low micromolar concentrations in vitro. These data define the structural basis of triclosan binding to PfENR and will facilitate structure-based optimization of PfENR inhibitors.

PubMed: 11792710
DOI: 10.1074/jbc.M112000200

実験手法

X-RAY DIFFRACTION (2.35 Å)