配体诱导炭疽毒素致死因子中S1'位点的扩张。
Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor.
作者信息
Maize Kimberly M, Kurbanov Elbek K, Johnson Rodney L, Amin Elizabeth Ambrose, Finzel Barry C
机构信息
Department of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, 8-101 Weaver-Densford Hall, Minneapolis, MN 55455, United States.
Department of Medicinal Chemistry, University of Minnesota, 308 Harvard St SE, 8-101 Weaver-Densford Hall, Minneapolis, MN 55455, United States.
出版信息
FEBS Lett. 2015 Dec 21;589(24 Pt B):3836-41. doi: 10.1016/j.febslet.2015.11.005. Epub 2015 Nov 11.
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.
炭疽杆菌致死因子（LF）是一种三联体外毒素的组成部分，在细菌初次感染后，对炭疽持续的细胞毒性负有部分责任。锌金属蛋白酶抑制剂已作为潜在治疗剂进行研究，但LF是一个具有挑战性的靶点，因为抑制剂缺乏足够的选择性或具有不良的药物性质。这些结构研究揭示了该酶的一种不同构象，由特定抑制剂结合诱导产生，该构象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机会。
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