Two engineered eglin c mutants potently and selectively inhibiting kexin or furin
文献类型：期刊论文
| 作者 | Liu, ZX; Fei, H; Chi, CW |
| 刊名 | FEBS LETTERS
 |
| 出版日期 | 2004 |
| 卷号 | 556期号:1页码:116-120 |
| 关键词 | eglin c proprotein convertase furin kexin mutation |
| 通讯作者 | Chi, CW (reprint author), Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,chi@sunm.shcne.ac.cn |
| 英文摘要 | Eglin c with mutants L45R and D42R at the P-1 and P-4 positions has been reported to become a stable inhibitor toward the proprotein convertases (PC), furin and kexin, with a K-i of 2.3 x 10(-8) and 1.3 x 10(-10) M, respectively. The mutant was further engineered at the P-2'-P-4' positions to create a more potent and selective inhibitor for each enzyme. The residue Asp at P-1' which is crucial for stabilizing the conformation of eglin c remained unchanged. The eglin c mutants cloned into the vector pGEX-2T and expressed in Escherichia coli (DH5alpha) were purified to homogeneity, and their inhibitory activities toward the purified recombinant furin and kexin were examined. The results showed that (1) Leu47 at P-2' replaced with either a positively or negatively charged residue resulted in a decrease in inhibitory activities to both enzymes; (2) the replacement of Arg with Asp at P-3' was favorable for inhibiting furin with a K-i of 7.8 x 10(-9) M, but not for inhibiting kexin; (3) the replacement of Tyr with Glu at P-4' increased the inhibitory activity to kexin with a K-i of 3 x 10(-11) M, but was almost without any influence on furin inhibition. It was indicated that the inhibitory specificity of eglin c could be changed from inhibiting elastase to inhibiting PCs by site-directed mutation at the P positions, while the inhibitory selectivity to furin or kexin could be optimized by mutation at the P' positions. (C) 2003 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. |
| 学科主题 | Biochemistry & Molecular Biology; Biophysics; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 关键词[WOS] | PROPROTEIN CONVERTASE FURIN ; PROCESSING PROTEASES ; FUSION GLYCOPROTEIN ; MEASLES-VIRUS ; CELL-SURFACE ; ACTIVATION ; CLEAVAGE ; YEAST ; PROTEINASES ; GENE |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000188125600022 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2199]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Liu, ZX,Fei, H,Chi, CW. Two engineered eglin c mutants potently and selectively inhibiting kexin or furin[J]. FEBS LETTERS,2004,556(1):116-120. |
| APA | Liu, ZX,Fei, H,&Chi, CW.(2004).Two engineered eglin c mutants potently and selectively inhibiting kexin or furin.FEBS LETTERS,556(1),116-120. |
| MLA | Liu, ZX,et al."Two engineered eglin c mutants potently and selectively inhibiting kexin or furin".FEBS LETTERS 556.1(2004):116-120. |
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