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Literature summary for 3.4.14.9 extracted from

  • Sole-Domenech, S.; Rojas, A.V.; Maisuradze, G.G.; Scheraga, H.A.; Lobel, P.; Maxfield, F.R.
    Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar Abeta by multiple endoproteolytic cleavages within the beta-sheet domain (2018), Proc. Natl. Acad. Sci. USA, 115, 1493-1498 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.4.14.9

Inhibitors

Inhibitors Comment Organism Structure
Ala-Ala-Phe-chloromethylketone AAF-CMK, inhibits both the endoproteolytic and tripeptidyl peptidase activities of TPP1 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
lysosome
-
 Homo sapiens 5764
-
lysosome microglial lysosomes Homo sapiens 5764
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
amyloid-beta + H2O Homo sapiens AbetaCy3 peptides are released from the nanofibrils due to TPP1 activity ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens O14773
-
-

Source Tissue

Source Tissue Comment Organism Textmining
microglia
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
amyloid-beta + H2O AbetaCy3 peptides are released from the nanofibrils due to TPP1 activity Homo sapiens ?
-
 ?
amyloid-beta1-42 + H2O the 34 Abeta end of the substrate shows integrated peak areas for peptide fragments 21-34, 22-34, and 23-34, indicative of cleavage after residue L34. The most abundant cleavages occur after residues Y10, G33, L34, and A30, and these cleavages occur more rapidly at pH 3.0 than at pH 4.5, consistent with endopeptidase activity. Peptides ending at residues E11, L17, F20, G37, and G38, are detected with lower abundances. At later times, the abundance of some of the peptides may decrease due to further proteolysis by TPP1. TPP1 can proteolyze monomeric Abeta1-42 efficiently at acidic pH Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
N-terminal tripeptidyl exopeptidase
-
 Homo sapiens
Tpp1
-
 Homo sapiens
tripeptidyl peptidase 1
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
3
-
 endopeptidase Homo sapiens
5
-
 N-terminal tripeptidyl exopeptidase Homo sapiens

pH Range

pH Minimum pH Maximum Comment Organism
3 4.5 higher endopeptidase activity at pH 3.0 compared to pH 4.5 Homo sapiens

General Information

General Information Comment Organism
additional information molecular dynamics (MD) simulations are used to analyze the effects of each cleavage on beta-sheet and fibril stability of amyloid-beta, eight cleavage sites are selected to be simulated, namely after residues K16, F20, G33, L34, M35, V36, G38, and V40, stability of hydrogen bonds following selected TPP1 cleavages and peptide release from the fibril, molecular modeling, detailed overview Homo sapiens
physiological function tripeptidyl peptidase 1 (TPP1) is a lysosomal serine protease, that possesses endopeptidase activity and cleaves peptides between hydrophobic residues. TPP1 is able to proteolyze fibrillar amyloid-beta efficiently. Mass spectrometry analysis of peptides released from fibrillar amyloid-beta digested with TPP1 reveals several endoproteolytic cleavages including some within beta-sheet regions that are important for fibril formation. These cleavages destabilize fibrillar beta-sheet structure. N-terminal tripeptidyl exopeptidase activity with a pH optimum of 5 that catalyzes the sequential release of tripeptides from the unsubstituted N termini of proteins Homo sapiens