Stieneke-Gröber A, Vey M, Angliker H, Shaw E, Thomas G, Roberts C, Klenk H D, Garten W
Institut für Virologie, Philipps-Universität Marburg, Germany.
EMBO J. 1992 Jul;11(7):2407-14. doi: 10.1002/j.1460-2075.1992.tb05305.x.
Many viruses have membrane glycoproteins that are activated at cleavage sites containing multiple arginine and lysine residues by cellular proteases so far not identified. The proteases responsible for cleavage of the hemagglutinin of fowl plague virus, a prototype of these glycoproteins, has now been isolated from Madin-Darby bovine kidney cells. The enzyme has a mol. wt of 85,000, a pH optimum ranging from 6.5 to 7.5, is calcium dependent and recognizes the consensus sequence R-X-K/R-R at the cleavage site of the hemagglutinin. Using a specific antiserum it has been identified as furin, a subtilisin-like eukaryotic protease. The fowl plague virus hemagglutinin was also cleaved after coexpression with human furin from cDNA by vaccinia virus vectors. Peptidyl chloroalkylketones containing the R-X-K/R-R motif specifically bind to the catalytic site of furin and are therefore potent inhibitors of hemagglutinin cleavage and fusion activity.
许多病毒具有膜糖蛋白，这些膜糖蛋白在含有多个精氨酸和赖氨酸残基的切割位点被尚未鉴定的细胞蛋白酶激活。负责切割这些糖蛋白原型——禽瘟病毒血凝素的蛋白酶，现已从马-达二氏牛肾细胞中分离出来。该酶的分子量为85,000，最适pH范围为6.5至7.5，依赖钙，并且在血凝素的切割位点识别共有序列R-X-K/R-R。使用特异性抗血清已将其鉴定为弗林蛋白酶，一种枯草杆菌蛋白酶样真核蛋白酶。禽瘟病毒血凝素在通过痘苗病毒载体与来自cDNA的人弗林蛋白酶共表达后也被切割。含有R-X-K/R-R基序的肽基氯烷基酮特异性结合弗林蛋白酶的催化位点，因此是血凝素切割和融合活性的有效抑制剂。
