Target type: molecularfunction
Catalysis of the hydrolysis of nonterminal peptide bonds in a polypeptide chain, occurring within a membrane. [GOC:jl, ISBN:0198506732]
Aspartic endopeptidase activity, intramembrane cleaving, refers to the catalytic activity of specific aspartic proteases that cleave peptide bonds within the transmembrane region of proteins. These enzymes are characterized by their ability to hydrolyze peptide bonds on the carboxyl side of aspartic acid residues, located within the lipid bilayer. The catalytic mechanism involves a pair of aspartic acid residues within the active site, which coordinate a water molecule for nucleophilic attack on the peptide bond. The intramembrane location of the cleavage site distinguishes this activity from other aspartic protease activities that occur in the aqueous environment. This activity plays a crucial role in various biological processes, including protein trafficking, signal transduction, and membrane protein maturation. For instance, presenilin, a key component of the γ-secretase complex, exhibits intramembrane aspartic endopeptidase activity, which is responsible for the cleavage of amyloid precursor protein (APP) within the transmembrane domain, generating amyloid-β peptides implicated in Alzheimer's disease. In addition, other intramembrane aspartic proteases, such as signal peptide peptidase (SPP), are involved in the processing of transmembrane proteins, removing signal sequences and facilitating their proper insertion into the membrane. The specific recognition and cleavage of substrates within the membrane environment highlights the unique role of intramembrane aspartic endopeptidases in maintaining cellular integrity and function.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Signal peptide peptidase-like 2A | A signal peptide peptidase-like 2A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8TCT8] | Homo sapiens (human) |
| Presenilin-2 | A presenilin-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49810] | Homo sapiens (human) |
| Nicastrin | A nicastrin that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92542] | Homo sapiens (human) |
| Signal peptide peptidase-like 2A | A signal peptide peptidase-like 2A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8TCT8] | Homo sapiens (human) |
| Presenilin-1 | A presenilin-1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P49768] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| tocopheroxy radical | tocopheroxy radical: RN given refers to radical ion (1+), (2R-(2R*(4R*,8R*)))-isomer; RN for cpd without isomeric designation not available 12/90 | tocopherol | |
| 7-amino-4-chloro-3-methoxy-2-benzopyran-1-one | isocoumarins | ||
| tarenflurbil | tarenflurbil: R-enantiomer of flurbiprofen but not a COX inhibitor; modulates NF-kB, gamma-secretase, amyloid beta-protein; | flurbiprofen | |
| cholanic acid | 5beta-cholanic acids; cholanic acid | ||
| t0901317 | T0901317: an LXRalpha and LXRbeta agonist | ||
| n-(n-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester | DAPT : A dipeptide consisting of alanylphenylglycine derivatised as a 3,5-difluorophenylacetamide at the amino terminal and a tert-butyl ester at the carboxy terminal. A gamma-secretase inhibitor. | carboxylic ester; difluorobenzene; dipeptide; tert-butyl ester | EC 3.4.23.46 (memapsin 2) inhibitor |
| sulindac sulfide | sulindac sulfide : An aryl sulfide that is a metabolite of sulindac. A non-steroidal anti-inflammatory drug, which also has anticancer activity. sulindac sulfide: sulfated analog of indomethacin & inhibitor of prostaglandin synthesis in vitro; RN given refers to cpd without isomeric designation; structure given in first source | aryl sulfide; monocarboxylic acid; organofluorine compound | antineoplastic agent; apoptosis inducer; non-steroidal anti-inflammatory drug |
| l 685458 | L 685458: a gamma-secretase inhibitor; structure in first source L-685,458 : A peptide and carboxamide that is L-leucyl-L-phenylalaninamide, L-Leu-L-Phe-NH2, which has been acylated on the N-terminus by a Phe-Phe hydroxyethylene dipeptide isotere, 2R-benzyl-5S-tert-butoxycarbonylamino-4R-hydroxy-6-phenylhexanoic acid. Compounds based on the structure of L-685,458 are potent inhibitors of gamma-secretase, which mediates the final catalytic step that generates the amyloid beta-peptide (Abeta), which assembles into the neurotoxic aggregates in the brains of sufferers of Alzheimer's disease. | carbamate ester; monocarboxylic acid amide; peptide; secondary alcohol | EC 3.4.23.46 (memapsin 2) inhibitor; peptidomimetic |
| mk 0752 | |||
| ly 450139 | peptide | ||
| chf 5074 | 1-(3',4'-dichloro-2-fluoro(1,1'-biphenyl)-4-yl)cyclopropanecarboxylic acid: a beta-amyloid(1-42) lowering agent; structure in first source | ||
| ly 411575 | dibenzoazepine; difluorobenzene; lactam; secondary alcohol | EC 3.4.23.46 (memapsin 2) inhibitor | |
| 4-(2-((1r)-1-(((4-chlorophenyl)sulfonyl)-2,5-difluoroanilino)ethyl)-5-fluorophenyl)butanoic acid | sulfonamide | ||
| begacestat | |||
| e 2012 | |||
| mrk 560 | MRK 560: a gamma-secretase inhibitor; MRK-560 is the (cis)-isomer; structure in first source | ||
| 1, 3-di-(n-carboxybenzoyl-leucyl-leucyl)amino acetone | 1, 3-di-(N-carboxybenzoyl-leucyl-leucyl)amino acetone: structure in first source | ||
| pf 3084014 | nirogacestat : A member of the class of imidazoles that is 1H-imidazole substituted by a 1-[(2,2-dimethylpropyl)amino]-2-methylpropan-2-yl group at position 1 and a {N-[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]-L-norvalyl}amino group at position 4. It is a gamma-secretase inhibitor whose hydrobromide salt is indicated for adult patients with progressing desmoid tumours who require systemic treatment. nirogacestat: an antineoplastic agent | ||
| bms 708163 | BMS 708163: structure in first source | oxadiazole; ring assembly | |
| ro 4929097 | dibenzoazepine; dicarboxylic acid diamide; lactam; organofluorine compound | EC 3.4.23.46 (memapsin 2) inhibitor | |
| jnj 40418677 | |||
| (r)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1h-pyrazolo(4,3-c)quinoline | (R)-4-cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo(4,3-c)quinoline: gamma secretase inhibitor; structure in first source |