{"database":"JPOST Repository","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Xlsx":["https://storage.jpostdb.org/JPST003762/files/SA_protein.xlsx","https://storage.jpostdb.org/JPST003762/files/WT_protein.xlsx"],"Raw":["https://storage.jpostdb.org/JPST003762/files/20240523_WT.raw","https://storage.jpostdb.org/JPST003762/files/20240523_SA.raw"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Genta Ito"],"species":["Escherichia Coli"],"full_dataset_link":["https://repository.jpostdb.org/entry/JPST003762"],"submitter_affiliation":["Teikyo University"],"sample_protocol":[""],"repository":["jPOST"],"data_protocol":[""],"pubmed_abstract":["Nonenzymatic D-isomerization of aspartic acid in proteins has been observed in lesions associated with age-related diseases, including cataracts and Alzheimer's disease. Given that D-isomerization of Asp disrupts the physiological conformation of proteins, it has been postulated that D-isomerization of Asp in proteins is a key factor in the pathogenesis of age-related diseases. D-Aspartyl endopeptidase (DAEP) activity, which cleaves proteins at the carboxy terminus of D-Asp and potentially induces degradation of abnormal proteins with D-isomerized Asp, has been observed in mitochondrial fractions of mammalian tissues. However, the specific proteins responsible for mammalian DAEP activity remain unknown. In this study, we identified mitochondrial serine β-lactamase-like protein (LACTB) as the first mammalian protein with DAEP activity by structural comparison with paenidase, a bacterial DAEP. LACTB exhibited DAEP activity similar to paenidase in an in vitro assay. In addition, LACTB cleaved a 10-residue peptide derived from amyloid β1-10 containing D-Asp at position 7, which was also observed with mammalian DAEP. LACTB has previously been characterized as a tumor suppressor and as a protein whose increased expression is associated with an increased risk of Alzheimer's disease. Therefore, our findings suggest that disruption of the proteostasis of D-Asp-containing proteins may underlie the pathogenesis of these diseases."],"pubmed_title":["Discovery and biochemical characterization of the D-aspartyl endopeptidase activity of the serine protease LACTB."],"pubmed_authors":["Ito Genta G, Utsunomiya-Tate Naoko N"],"additional_accession":[]},"is_claimable":false,"name":"Identification of proteins present in LACTB solutions overexpressed and purified from E.coli by LC-MS/MS.","description":"Non-enzymatic D-isomerization of aspartic acid in proteins has been observed in lesions associated with age-related diseases, including cataracts and Alzheimer's disease. Since D-isomerization of Asp disrupts the physiological conformation of proteins, it has been postulated that D-isomerization of Asp in proteins is a key factor in the pathogenesis of age-related diseases. D-aspartyl endopeptidase (DAEP) activity, which cleaves proteins at the carboxy terminus of D-Asp and may induce degradation of abnormal proteins with D-isomerized Asp, has been observed in mitochondrial fractions of mammalian tissues. However, the specific proteins responsible for mammalian DAEP activity remain unknown. In this study, we identified serine beta-lactamase-like protein (LACTB) as a mammalian D-aspartyl endopeptidase. We overexpressed and purified LACTB from E. coli and found that wild-type LACTB exhibited DAEP activity, but the S164A mutant LACTB, which lacks the catalytic serine, did not. To confirm that there are no other proteins that could explain the difference in DAEP activity, we systematically identified proteins present in the purified solution of LACTB.","dates":{"publication":"Sat Apr 19 00:00:00 BST 2025"},"accession":"PXD062910","cross_references":{"TAXONOMY":["562"],"pubmed":["40286848"]}}