Structure—activity relationships in human interleukin-1α: identification of key residues for expression of biological activities
| Autor: | Michiko Yamayoshi, Junichi Yamagishi, Toshikazu Fukui, Mayumi Ohue, Hitoshi Kawashima, Masaaki Yamada, Hirotada Kotani |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Cytotoxicity
Immunologic Molecular Sequence Data Mutant Bioengineering Sequence alignment Biology Lymphocyte Activation medicine.disease_cause Biochemistry Dinoprostone Structure-Activity Relationship Aspartic acid medicine Humans Amino Acid Sequence Prostaglandin E2 Site-directed mutagenesis Molecular Biology Escherichia coli chemistry.chemical_classification Binding Sites Base Sequence Biological activity Recombinant Proteins Amino acid chemistry Mutation Mutagenesis Site-Directed Sequence Alignment Interleukin-1 Biotechnology medicine.drug |
| Zdroj: | "Protein Engineering, Design and Selection". 5:171-176 |
| ISSN: | 1741-0134 1741-0126 |
| DOI: | 10.1093/protein/5.2.171 |
| Popis: | To identify the sites important for the different biological activities of human interleukin-1 alpha (hIL-1 alpha), 56 single-amino acid-substituted mutants of hIL-1 alpha were produced in Escherichia coli using site-directed mutagenesis, and were examined for their biological activities such as mouse lymphocyte activating factor activity (LAF activity), cytostatic activity against human melanoma cells A-375 (A375 activity) and prostaglandin E2 (PGE2) inducing activity in human osteosarcoma cells MG-63 (PEI activity). Two amino acid residues, Asp26 and Asp151, were found to be important for these activities. The replacement of Asp26 by Val caused a decrease in LAF and PEI activities by one or two orders of magnitude and a slight decrease in A375 activity. The Tyr or Phe substitution for Asp151 caused decreases in LAF and A375 activities by one or two orders of magnitude and complete loss of PEI activity. The change from Asp151 to Lys or Arg resulted in marked decrease in LAF activity and complete loss of A375 and PEI activities. Since Asp26 and Asp151 are close to each other in the three-dimensional structure, the region involving these amino acids seems to be important for the biological activities of hIL-1 alpha. |
| Databáze: | OpenAIRE |
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