4DV8

Anthrax Lethal Factor metalloproteinase in complex with the Hydroxamic acid based small molecule PT8421

4DV8 の概要

• エントリーDOI: 10.2210/pdb4dv8/pdb
• 分子名称: Lethal factor, ZINC ION, (2S)-6-[(4-fluorobenzyl)amino]-2-[(2R)-2-(4-fluorophenyl)-2-methoxyethyl]-N-hydroxyhexanamide, ... (5 entities in total)
• 機能のキーワード: endopeptidase, zinc dependent, hydrolase
• 由来する生物種: Bacillus anthracis (anthrax,anthrax bacterium)
• 細胞内の位置: Secreted: P15917
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 61965.03

構造登録者

Margosiak, S.A.,Sankaran, B. (登録日: 2012-02-22, 公開日: 2012-03-14, 最終更新日: 2024-02-28)

主引用文献

Jiao, G.S.,Kim, S.,Moayeri, M.,Crown, D.,Thai, A.,Cregar-Hernandez, L.,McKasson, L.,Sankaran, B.,Lehrer, A.,Wong, T.,Johns, L.,Margosiak, S.A.,Leppla, S.H.,Johnson, A.T.
Antidotes to anthrax lethal factor intoxication. Part 3: Evaluation of core structures and further modifications to the C2-side chain.
Bioorg.Med.Chem.Lett., 22:2242-, 2012

PubMed Abstract: Four core structures capable of providing sub-nanomolar inhibitors of anthrax lethal factor (LF) were evaluated by comparing the potential for toxicity, physicochemical properties, in vitro ADME profiles, and relative efficacy in a rat lethal toxin (LT) model of LF intoxication. Poor efficacy in the rat LT model exhibited by the phenoxyacetic acid series (3) correlated with low rat microsome and plasma stability. Specific molecular interactions contributing to the high affinity of inhibitors with a secondary amine in the C2-side chain were revealed by X-ray crystallography.

PubMed: 22342144
DOI: 10.1016/j.bmcl.2012.01.095

実験手法

X-RAY DIFFRACTION (1.632 Å)