The processing of Alzheimer A4/beta-amyloid protein precursor: identification of a human brain metallopeptidase which cleaves -Lys-Leu- in a model peptide

Biochem Biophys Res Commun. 1991 Sep 30;179(3):1148-54. doi: 10.1016/0006-291x(91)91691-5.


A search for human brain peptidases with the specificity to cleave the 695 residue A4/beta amyloid precursor protein within the -Gln-Lys-Leu- (611-613) sequence was carried out using carbobenzoxy-Gln-Lys-Leu-p-nitroanilide as substrate. A metalloendopeptidase was identified in the soluble fraction of post mortem human cerebral cortex which cleaves the substrate at the Lys-Leu bond. The enzyme was partially purified by anion exchange and size exclusion chromatography; it has a Mr of approximately 105-120 kda, is inhibited by EDTA but can be reactivated by Mn++ ions, and has maximum activity between pH 6.8 and 8.

MeSH terms

  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / genetics
  • Amino Acid Sequence
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Brain / enzymology*
  • Chromatography, Gel
  • Chromatography, High Pressure Liquid
  • Chromatography, Ion Exchange
  • Humans
  • Kinetics
  • Leucine*
  • Lysine*
  • Metalloendopeptidases / isolation & purification
  • Metalloendopeptidases / metabolism*
  • Molecular Sequence Data
  • Peptides / chemical synthesis*
  • Protein Processing, Post-Translational*
  • Substrate Specificity


  • Amyloid beta-Protein Precursor
  • Peptides
  • Metalloendopeptidases
  • Leucine
  • Lysine