Limitations in current acetylcholinesterase structure-based design of oxime antidotes for organophosphate poisoning.
Limitations in current acetylcholinesterase structure-based design of oxime antidotes for organophosphate poisoning.
复制标题
DOI：
10.1111/nyas.13128
复制
发表时间：
2016-08
影响因子：
5.2
通讯作者：
Radić Z
中科院分区：
文献类型：
--
作者：
Kovalevsky A;Blumenthal DK;Cheng X;Taylor P;Radić Z
Acetylcholinesterase (AChE; EC 3.1.1.7), an essential enzyme of cholinergic neurotransmission in vertebrates, is a primary target in acute nerve agent and organophosphate (OP) pesticide intoxication. Catalytically inactive OP–AChE conjugates formed between the active-center serine and phosphorus of OPs can, in principle, be reactivated by nucleophilic oxime antidotes. Antidote efficacy is limited by the structural diversity of OP–AChE conjugates resulting from differences in the structure of the conjugated OP, the different active-center volumes they occupy when conjugated to the active-center serine of AChE, and the distinct chemical characteristics of both OPs and oximes, documented in numerous X-ray structures of OP-conjugated AChEs. Efforts to improve oxime reactivation efficacy by AChE structure–based enhancement of oxime structure have yielded only limited success. We outline here potential limitations of available AChE X-ray structures that preclude an accurate prediction of oxime structures, which are necessary for association in the OP–AChE gorge and nucleophilic attack of the OP-conjugated phosphorus.
登录
查看更多内容
影响因子：
3.8
作者：
Ringe, D;Petsko, GA
通讯作者：
Petsko, GA
影响因子：
2.9
作者：
Bartolucci, C;Perola, E;Lamba, D
通讯作者：
Lamba, D
影响因子：
4.8
作者：
Boyd, AE;Dunlop, CS;Johnson, DA
通讯作者：
Johnson, DA
影响因子：
4.8
作者：
Shi, JX;Boyd, AE;Taylor, P
通讯作者：
Taylor, P
影响因子：
5.1
作者：
Thiermann, Horst;Worek, Franz;Kehe, Kai
通讯作者：
Kehe, Kai