Jank Thomas, Giesemann Torsten, Aktories Klaus
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Otto-Krayer-Haus, Albertstrasse 25, D-79104 Freiburg, Germany.
Glycobiology. 2007 Apr;17(4):15R-22R. doi: 10.1093/glycob/cwm004. Epub 2007 Jan 19.
Clostridium difficile causes pseudomembranous colitis and is responsible for many cases of nosocomial antibiotic-associated diarrhea. Major virulence factors of C. difficile are the glucosylating exotoxins A and B. Both toxins enter target cells in a pH- dependent manner from endosomes by forming pores. They translocate the N-terminal catalytic domains into the cytosol of host cells and inactivate Rho guanosine triphosphatases by glucosylation. The crystal structure of the catalytic domain of toxin B was solved in a complex with uridine diphosphate, glucose, and manganese ion, exhibiting a folding of type A family glycosyltransferases. Crystallization of fragments of the C-terminus of toxin A, which is characterized by polypeptide repeats, revealed a solenoid-like structure often found in bacterial cell surface proteins. These studies, which provide new insights into structure, uptake, and function of the family of clostridial glucosylating toxins, are reviewed.
艰难梭菌可引发伪膜性结肠炎，也是许多医院获得性抗生素相关性腹泻病例的病因。艰难梭菌的主要毒力因子是糖基化外毒素A和B。两种毒素均通过在内体中形成孔道，以pH依赖的方式进入靶细胞。它们将N端催化结构域转运至宿主细胞的胞质溶胶中，并通过糖基化使Rho鸟苷三磷酸酶失活。毒素B催化结构域的晶体结构在与二磷酸尿苷、葡萄糖和锰离子形成的复合物中得到解析，呈现出A类家族糖基转移酶的折叠形式。以多肽重复为特征的毒素A C端片段的结晶显示出一种常在细菌细胞表面蛋白中发现的螺线管样结构。本文对这些研究进行了综述，这些研究为梭菌糖基化毒素家族的结构、摄取和功能提供了新的见解。
