Fan Erkang, O'Neal Claire J, Mitchell Daniel D, Robien Mark A, Zhang Zhongsheng, Pickens Jason C, Tan Xiao-Jian, Korotkov Konstantin, Roach Claudia, Krumm Brian, Verlinde Christophe L M J, Merritt Ethan A, Hol Wim G J
Department of Biochemistry, Biomolecular Structure Center, University of Washington, Box 357742, Seattle WA 98195, USA.
Int J Med Microbiol. 2004 Oct;294(4):217-23. doi: 10.1016/j.ijmm.2004.07.002.
Structural biology studies on cholera toxin and the closely related heat-labile enterotoxin from enterotoxigenic Escherichia coli over the past decade have shed light on the mechanism of toxin action at molecular and atomic levels. Also, components of the extracellular protein secretion apparatus that translocate the toxins across the outer membrane are being investigated. At the same time, structure-based design has led to various classes of compounds targeting different toxin sites, including highly potent multivalent inhibitors that block the toxin receptor-binding process.
在过去十年中,针对霍乱毒素以及产肠毒素大肠杆菌中密切相关的不耐热肠毒素开展的结构生物学研究,在分子和原子水平上揭示了毒素的作用机制。此外,正在对将毒素转运穿过外膜的细胞外蛋白质分泌装置的组成部分进行研究。与此同时,基于结构的设计已产生了针对不同毒素位点的各类化合物,包括能阻断毒素受体结合过程的高效多价抑制剂。