6SBR

The crystal structure of PfA-M1 in complex with 7-amino-1,4-dibromo-5,7,8,9-tetrahydrobenzocyclohepten-6-one

6SBR の概要

• エントリーDOI: 10.2210/pdb6sbr/pdb
• 分子名称: M1-family alanyl aminopeptidase, ZINC ION, [(7~{S})-1,4-bis(bromanyl)-6,6-bis(oxidanyl)-5,7,8,9-tetrahydrobenzo[7]annulen-7-yl]azanium, ... (7 entities in total)
• 機能のキーワード: m1 aminopeptidase, hydrolase
• 由来する生物種: Plasmodium falciparum (isolate 3D7)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 108445.09

構造登録者

Salomon, E.,Schmitt, M.,Mouray, E.,McEwen, A.G.,Torchy, M.,Poussin-Courmontagne, P.,Alavi, S.,Tarnus, C.,Cavarelli, J.,Florent, I.,Albrecht, S. (登録日: 2019-07-22, 公開日: 2020-03-25, 最終更新日: 2024-01-24)

主引用文献

Salomon, E.,Schmitt, M.,Mouray, E.,McEwen, A.G.,Bounaadja, L.,Torchy, M.,Poussin-Courmontagne, P.,Alavi, S.,Tarnus, C.,Cavarelli, J.,Florent, I.,Albrecht, S.
Aminobenzosuberone derivatives as PfA-M1 inhibitors: Molecular recognition and antiplasmodial evaluation.
Bioorg.Chem., 98:103750-103750, 2020

PubMed Abstract: Aminobenzosuberone-based PfA-M1 inhibitors were explored as novel antimalarial agents against two different Plasmodium falciparum strains. The 4-phenyl derivative 7c exhibited the most encouraging growth inhibitory activity with IC values of 6.5-11.2 µM. X-ray crystal structures and early assessment of DMPK/ADME-Tox parameters allowed us to initiate structure-based drug design approach and understand the liabilities (such as potential metabolic and aqueous solubility issues) as well as identify the opportunities for improvement of this aminobenzosuberone series. It also suggested that compound 7c should be regarded as an attractive chemical tool to investigate the different biological roles of this multifunctional PfA-M1 protein.

PubMed: 32182520
DOI: 10.1016/j.bioorg.2020.103750

実験手法

X-RAY DIFFRACTION (1.54 Å)