Inhibition of human matriptase by eglin c variants
Inhibition of human matriptase by eglin c variants
复制标题
DOI：
10.1016/j.febslet.2006.03.030
复制
发表时间：
2006-04-17
期刊：
影响因子：
3.5
通讯作者：
Leduc, R
中科院分区：
文献类型：
--
作者：
Désilets, A;Longpré, JM;Leduc, R
基于matriptase的酶特异性，一种在上皮肿瘤中过表达的II型跨膜丝氨酸蛋白酶（TTSP），我们筛选了表达蛋白酶抑制剂eglin c变体的cDNA文库，以鉴定有效的matriptase抑制剂。其中最有效的是R1 K4 '-eglin，其野生型Pro（45）（P1位置）和Tyr（49）（P4'位置）残基分别被Arg和LyS取代，导致产生选择性、高亲和力（Ki为4）和蛋白质水解稳定的matriptase抑制剂。筛选eglin c变体可以产生间质蛋白酶和TTSP家族其他成员的特异性、有效和稳定的抑制剂。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Based on the enzyme specificity of matriptase, a type II transmembrane serine protease (TTSP) overexpressed in epithelial tumors, we screened a cDNA library expressing variants of the protease inhibitor eglin c in order to identify potent matriptase inhibitors. The most potent of these, R1K4'-eglin, which had the wild-type Pro(45) (P1 position) and Tyr(49) (P4' position) residues replaced with Arg and Lys, respectively, led to the production of a selective, high affinity (K-i of 4 nM) and proteolytically stable inhibitor of matriptase. Screening for eglin c variants could yield specific, potent and stable inhibitors to matriptase and to other members of the TTSP family. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.