A site-directed mutagenesis study on the role of isoleucine-23 of human epidermal growth factor in the receptor binding

Hiroshi Koide, Yutaka Muto, Hidefumi Kasai, Kaoru Kohri, Kumiko Hoshi, Seizo Takahashi, Ken ichi Tsukumo, Tetsuyuki Sasaki, Takanori Oka, Tetsuo Miyake, Tohru Fuwa, Daisuke Kohda, Fuyuhiko Inagaki, Tatsuo Miyazawa, Shigeyuki Yokoyama

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The isoleucine-23 residue of human epidermal growth factor (hEGF) was substituted by a variety of amino acid residues and the receptor-binding activities of variant hEGFs were determined by the use of human KB cell. Tight receptor binding was found of variants with hydrophobic amino acid residues in position 23. The size of the isoleucine residue was nearly optimum for the receptor binding as compared with other hydrophobic residues. The structure analysis by two-dimensional nuclear magnetic resonance spectroscopy showed that the substitution at position 23 only slightly affected the tertiary structure of hEGF. These indicate that the side chain of isoleucine residue in position 23, which is exposed on the protein surface, directly binds to a hydrophobic pocket of the receptor.

Original languageEnglish
Pages (from-to)257-261
Number of pages5
JournalBiochimica et Biophysica Acta (BBA)/Protein Structure and Molecular
Volume1120
Issue number3
DOIs
Publication statusPublished - 1992 Apr 17
Externally publishedYes

Keywords

  • Epidermal growth factor
  • Human epidermal growth factor receptor
  • NMR
  • Protein engineering
  • Site-directed mutagenesis

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology

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  • Cite this

    Koide, H., Muto, Y., Kasai, H., Kohri, K., Hoshi, K., Takahashi, S., Tsukumo, K. I., Sasaki, T., Oka, T., Miyake, T., Fuwa, T., Kohda, D., Inagaki, F., Miyazawa, T., & Yokoyama, S. (1992). A site-directed mutagenesis study on the role of isoleucine-23 of human epidermal growth factor in the receptor binding. Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular, 1120(3), 257-261. https://doi.org/10.1016/0167-4838(92)90245-9