Studies on receptor binding site of insulin: The hydrophobic B12Val can be substituted by hydrophilic Thr
| Autor: | Qiong-qing Wang, You-shang Zhang, You-min Feng |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Threonine
Swine Placenta medicine.medical_treatment Clinical Biochemistry Mutant Saccharomyces cerevisiae Biochemistry Chemical synthesis Structure-Activity Relationship Residue (chemistry) Leucine Insulin receptor substrate Genetics medicine Animals Humans Molecular Biology Binding Sites biology Chemistry Insulin Mutagenesis Valine Biological activity Cell Biology Receptor Insulin Insulin receptor Mutagenesis Site-Directed biology.protein Proinsulin |
| Zdroj: | IUBMB Life. 39:1245-1254 |
| ISSN: | 1521-6543 |
| DOI: | 10.1080/15216549600201442 |
| Popis: | Summary: [B12Thr]human insulin and [Bl2Leu]human insulin were obtained by means of site-directed random mutagenesis. [B12Thr]human insulin retains total biological activity but [B 12Leu]human insulin has much lower biological activity. Receptor binding activities of [B 12Thr]human insulin and [B 12Leu]human insulin are 56% and 3%, respectively, as that of native porcine insulin. The results suggest that the hydrophobic property of the residue side chain at B12 may not be necessary. The three-dimensional structure of insulin shows that in the monomer the side chains ofB12Val, B16Tyr, B24Phe and B25Phe form a hydrophobic surface [12]. This hydrophobic surface was proposed to be a key constituent part of the receptor binding site of insulin[3-6]. It is interesting to study the role of B 12Val in the structure and function of insulin since it is a constituent residue of the hydrophobic surface and it is also conserved in insulins from different species[7]. Schwartz and Hu reported that insulin analogs, in which BI2Val was substituted by Asn, Phe or cz-aminoisobutyric acid by means of chemical synthesis, had much lower biological activities than native insulin [8-9]. Similarly when B 12Val was substituted by Ile or Glu, the biological activity of these analogs was greatly reduced [10]. For further understanding the role of the residue at position B 12 in the receptor binding site of insulin, we have prepared, by means of sitedirected random mtagensis, two mutants of porcine insulin precursor(PIP) in |
| Databáze: | OpenAIRE |
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