Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor.
Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor.
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DOI：
10.1016/j.febslet.2015.11.005
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发表时间：
2015-12-21
期刊：
影响因子：
3.5
通讯作者：
Finzel BC
中科院分区：
文献类型：
--
作者：
Maize KM;Kurbanov EK;Johnson RL;Amin EA;Finzel BC
炭疽杆菌致死因子（Bacillusanthracis lethal factor，LF）是炭疽杆菌感染后产生持续细胞毒性的三重外毒素之一。锌金属蛋白酶抑制剂已被研究作为潜在的治疗剂，但LF是一个具有挑战性的目标，因为抑制剂缺乏足够的选择性或具有不良的药物特性。这些结构研究揭示了酶的另一种构象，在特异性抑制剂结合后诱导，打开了一个以前未观察到的称为S1′* 的深口袋，这可能为设计靶向该亚位点的选择性抑制剂提供新的机会。
The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1′* which might afford new opportunities to design selective inhibitors that target this subsite.