The inhibitory activities of recombinant eglin C mutants on kexin and furin, using site-directed mutagenesis and molecular modeling
文献类型：期刊论文
| 作者 | Fei, H; Luo, MJ; Ye, YZ; Ding, DF; Chi, CW |
| 刊名 | ACTA BIOCHIMICA ET BIOPHYSICA SINICA
 |
| 出版日期 | 2001 |
| 卷号 | 33期号:6页码:591-599 |
| 关键词 | proprotein convertase proteinase inhibitor site-directed mutagenesis molecular modeling |
| 通讯作者 | , |
| 英文摘要 | Mammalian furin and yeast kexin are members of the proprotein convertase family involved in the proteolytic processing of many important precursor proteins. Here the gene coding for the subtilisin inhibitor eglin C was totally synthesized and expressed in E. coli. Substitution of residues at each position P-1, P-2 and P-4 of eglin C with a basic residue using protein engineering could make eglin C a very strong inhibitor for furin (K-i around 10(-9) mol/L), and even more strong for kexin (K-i around 10(-11) mol/L). Results indicated that: (1) A basic residue Lys or Arg at P-1 site is prerequisite for the inhibitor. (2) The second mutation with basic residue at P-4 site drastically increase the inhibitory activity by two orders of magnitude. (3) A basic residue at P-2 site is favorable for the binding to the enzyme, but unfavorable for the stability of the inhibitor, resulting in a temporary inhibition. (4) A hydrophobic residue is preferential at P-3 site. Based on the known crystal structures of subtilisin and eglin C, the interaction between the enzyme and inhibitor was modeled, and their involved residues were predicted which gave a good explanation to the experimental results. |
| 学科主题 | Biochemistry & Molecular Biology ; Biophysics |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biophysics |
| 关键词[WOS] | PROPROTEIN CONVERTASES ; SPECIFICITY ; ENDOPROTEASE ; ACTIVATION ; CLEAVAGE ; PROTEASE ; GENE ; GLYCOPROTEIN ; PRECURSOR ; PEPTIDES |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000172362600001 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2683]  |
| 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 | Fei, H,Luo, MJ,Ye, YZ,et al. The inhibitory activities of recombinant eglin C mutants on kexin and furin, using site-directed mutagenesis and molecular modeling[J]. ACTA BIOCHIMICA ET BIOPHYSICA SINICA,2001,33(6):591-599. |
| APA | Fei, H,Luo, MJ,Ye, YZ,Ding, DF,&Chi, CW.(2001).The inhibitory activities of recombinant eglin C mutants on kexin and furin, using site-directed mutagenesis and molecular modeling.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,33(6),591-599. |
| MLA | Fei, H,et al."The inhibitory activities of recombinant eglin C mutants on kexin and furin, using site-directed mutagenesis and molecular modeling".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 33.6(2001):591-599. |
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