Structure prediction of protease inhibitor region in amyloid precursor protein of Alzheimer's disease

K. Toma, N. Kitaguchi, H. Ito

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Recent findings of the protease inhibitor domain in amyloid precursor protein of Alzheimer's disease (APPI) raised a novel hypothesis on the mechanism of amyloid deposition in the brain. APPI has significant amino acid sequence homology with Kunitz-type basic trypsin inhibitor superfamily proteins, and the gene expression product showed real inhibitory activity. Since the three-dimensional model of APPI would help in understanding biological phenomena in molecular detail, we constructed an atomic model of APPI based on the structure of bovine pancreatic trypsin inhibitor (BPTI). The substitution of BPTI side chains by best-fitting corresponding amino acid structures was followed by the removal of van der Waals overlapping by molecular mechanics energy minimization with the AMBER force field, to give the feasible model of APPI. We also built serine protease models based on the structure of trypsin and investigated the target enzyme specificity of the inhibitory activity by the active-site mapping method. The models can explain the relative enzyme spectra of APPI and BPTI.

Original languageEnglish
Pages (from-to)202-205
Number of pages4
JournalJournal of Molecular Graphics
Volume7
Issue number4
DOIs
Publication statusPublished - 12-1989

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

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