The processing of Alzheimer A4/beta-amyloid protein precursor: identification of a human brain metallopeptidase which cleaves -Lys-Leu- in a model peptide.
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.
MRC Neurochemical Pathology Unit, Newcastle General Hospital, UK.
J R
JR
McDermott
A M
AM
Gibson
D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D006801:Humans; D007700:Kinetics; D007930:Leucine; D008239:Lysine; D008666:Metalloendopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity
D016564:Amyloid beta-Protein Precursor; D010455:Peptides; D008666:Metalloendopeptidases; D007930:Leucine; D008239:Lysine