Replacement of the interchain disulfide bridge-forming amino acids A7 and B7 by glutamate impairs the structure and activity of insulin
| LEADER | caa a22 4500 | ||
|---|---|---|---|
| 001 | 378895974 | ||
| 003 | CHVBK | ||
| 005 | 20180305123506.0 | ||
| 007 | cr unu---uuuuu | ||
| 008 | 161128e20041201xx s 000 0 eng | ||
| 024 | 7 | 0 | |a 10.1515/BC.2004.151 |2 doi |
| 035 | |a (NATIONALLICENCE)gruyter-10.1515/BC.2004.151 | ||
| 245 | 0 | 0 | |a Replacement of the interchain disulfide bridge-forming amino acids A7 and B7 by glutamate impairs the structure and activity of insulin |h [Elektronische Daten] |c [Zhan-Yun Guo, Xiao-Yuan Jia, You-Min Feng] |
| 520 | 3 | |a Insulin contains three disulfide bonds, one intrachain bond, A6-A11, and two interchain bonds, A7-B7 and A20-B19. Site-directed mutagenesis results (the two cysteine residues of disulfide A7-B7 were replaced by serine) showed that disulfide A7-B7 is crucial to both the structure and activity of insulin. However, chemical modification results showed that the insulin analogs still retained relatively high biological activity when A7Cys and B7Cys were modified by chemical groups with a negative charge. Did the negative charge of the modification groups restore the loss of activity and/or the disturbance of structure of these insulin analogs caused by deletion of disulfide A7-B7? To answer this question, an insulin analog with both A7Cys and B7Cys replaced by Glu, which has a long side-chain and a negative charge, was prepared by protein engineering, and its structure and activity were analyzed. Both the structure and activity of the present analog are very similar to that of the mutant with disulfide A7-B7 replaced by Ser, but significantly different from that of wild-type insulin. The present results suggest that removal of disulfide A7-B7 will result in serious loss of biological activity and the native conformation of insulin, even if the disulfide is replaced by residues with a negative charge. | |
| 540 | |a ©2004 by Walter de Gruyter Berlin New York | ||
| 690 | 7 | |a Biochemistry |2 nationallicence | |
| 690 | 7 | |a Molecular biology |2 nationallicence | |
| 690 | 7 | |a Cellular biology |2 nationallicence | |
| 690 | 7 | |a activity |2 nationallicence | |
| 690 | 7 | |a disulfide bond |2 nationallicence | |
| 690 | 7 | |a folding |2 nationallicence | |
| 690 | 7 | |a insulin |2 nationallicence | |
| 690 | 7 | |a structure |2 nationallicence | |
| 700 | 1 | |a Guo |D Zhan-Yun |u Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, PR China |4 aut | |
| 700 | 1 | |a Jia |D Xiao-Yuan |u Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, PR China |4 aut | |
| 700 | 1 | |a Feng |D You-Min |u Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, PR China |4 aut | |
| 773 | 0 | |t Biological Chemistry |d Walter de Gruyter |g 385/12(2004-12-01), 1171-1175 |x 1431-6730 |q 385:12<1171 |1 2004 |2 385 |o bchm | |
| 856 | 4 | 0 | |u https://doi.org/10.1515/BC.2004.151 |q text/html |z Onlinezugriff via DOI |
| 908 | |D 1 |a research article |2 jats | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1515/BC.2004.151 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Guo |D Zhan-Yun |u Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, PR China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Jia |D Xiao-Yuan |u Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, PR China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Feng |D You-Min |u Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, PR China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Biological Chemistry |d Walter de Gruyter |g 385/12(2004-12-01), 1171-1175 |x 1431-6730 |q 385:12<1171 |1 2004 |2 385 |o bchm | ||
| 900 | 7 | |b CC0 |u http://creativecommons.org/publicdomain/zero/1.0 |2 nationallicence | |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-gruyter | ||