An aminopeptidase from Streptomyces sp. KK565 degrades beta amyloid monomers, oligomers and fibrils.
The accumulation of beta amyloid (Aβ) has been a primary target for Alzheimer disease therapeutic strategies. Previously, we discovered an activity from Streptomyces sp. KK565 growth media that inhibits Aβ aggregation. The active component was an aminopeptidase and named Streptomyces sp. KK565 aminopeptidase (SKAP). SKAP cleaved N-terminal amino-acids of Aβ(1-42) monomer, inhibited formation of fibrils and protected Aβ(1-42)-induced neurotoxicity. Over-expression of a human homolog of SKAP, glutamate carboxypeptidase II (hGCPII) in Aβ-oversynthesizing cells dramatically reduced the Aβ levels. These findings suggest a possible role of M28 family peptidases in preventing Aβ deposits in mammalian brain.
Yoo
Chulbae
C
Division of Brain Diseases, National Institute of Health, Korea Center for Disease Control and Prevention, Seoul, Republic of Korea.
Ahn
Kyungsook
K
Park
Jeong Eun
JE
Kim
Min-Ju
MJ
Jo
Sangmee Ahn
SA
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D005798:Genes, Bacterial; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000633:toxicity; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013302:Streptomyces / Q000201:enzymology* / Q000235:genetics; D013379:Substrate Specificity
D016229:Amyloid beta-Peptides; D000954:Antigens, Surface; D001426:Bacterial Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011994:Recombinant Proteins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D000626:Aminopeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II