Identification of the cleavage sites of transforming growth factor α by insulin-degrading enzymes

Frederick G. Hamel, Barry D. Gehm, Marsha Rich Rosner, William C. Duckworth

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Insulin-degrading enzyme (IDE) is a sulfhydryl-dependent metalloproteinase with a zinc binding site unique to a new class of proteinases. The enzyme is relatively specific for a number of hormones/growth factors, such as insulin, atrial natriuretic peptide, IGF-II, and proinsulin. In this study we have identified the amino-acid bonds cleaved by IDE in transforming growth factor-α. High-performance liquid chromatography was used to separate the peptides generated by the degradation of 125I-TGF-α. The peptides were then submitted to sequential Edman degradation to determine the peptide bond broken. Cleavage sites were found at amino acids, 10-11 (Asp-Ser), 25-26 (Val-Gln), 28-29 (Asp-Lys), and 30-31 (Pro-Ala). In agreement with studies of cleavage sites of other hormones by this enzyme, no clear amino-acid specificity was seen. However, examination of the sites on a three-dimensional model of TGF-α suggest the primary mechanism used by IDE for determining cleavage sites is the tertiary structure of the substrate.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
Issue number2
StatePublished - Apr 4 1997


  • Insulin-degrading enzyme
  • Insulysin
  • Metalloproteinase
  • Sulfhydryl
  • Transforming growth factor α
  • Zinc binding site

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology


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