Purification and characterization of a novel metalloprotease from human brain with the ability to cleave substrates derived from the N-terminus of beta-amyloid protein.
The main component of amyloid plaques in Alzheimer's disease (AD) is the beta-amyloid peptide (beta/A4), derived from beta-amyloid precursor proteins (beta-APPs). In order to identify proteases possibly involved in the cleavage at the N-terminal site of beta/A4 a chromogenic peptide corresponding to this region of beta-APP was used. Here the purification and characterization of a new human brain protease with the ability to cleave the beta-APP peptide as well as beta-APP in vitro are described. The enzyme has a molecular mass of 100 kDa and belongs likely to the class of metalloproteases. It should further be named "MP100". The enzyme has a very broad substrate specificity in vitro.
Schönlein
C
C
Pharma Division, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Löffler
J
J
Huber
G
G
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D006801:Humans; D008666:Metalloendopeptidases / Q000302:isolation & purification* / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity
D000596:Amino Acids; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008666:Metalloendopeptidases