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Target
Gamma-secretase subunit APH-1A/Gamma-secretase subunit PEN-2/Nicastrin [34-709]/Presenilin-1
Ligand
BDBM28998
Substrate
Beta amyloid A4 protein
Meas. Tech.
Cell-Based Assay for Amyloid-beta Accumulation
EC50
12±n/a nM
Citation
 Bergstrom, CP; Sloan, CP; Lau, WY; Smith, DW; Zheng, M; Hansel, SB; Polson, CT; Corsa, JA; Barten, DM; Felsenstein, KM; Roberts, SB Carbamate-appended N-alkylsulfonamides as inhibitors of gamma-secretase. Bioorg Med Chem Lett 18:464-8 (2008) [PubMed]  Article 
Target
Name:
Gamma-secretase subunit APH-1A/Gamma-secretase subunit PEN-2/Nicastrin [34-709]/Presenilin-1
Synonyms:
Gamma-Secretase
Type:
Multi-subunit protease complex
Mol. Mass.:
n/a
Description:
A complex composed of a presenilin homodimer, nicastrin, APH1 and PEN2. It is the minimal complex sufficient for secretase activity.
Components:
This complex has 4 components.
Component 1
Name:
Gamma-secretase subunit APH-1A
Synonyms:
APH-1a | APH1A | APH1A_HUMAN | Aph-1alpha | Gamma-Secretase Subunit APH-1A | PSF | Presenilin-stabilization factor
Type:
Enzyme subunit; multi-pass membrane protein
Mol. Mass.:
28998.73
Organism:
Homo sapiens (Human)
Description:
n/a
Residue:
265
Sequence:
MGAAVFFGCTFVAFGPAFALFLITVAGDPLRVIILVAGAFFWLVSLLLASVVWFILVHVTDRSDARLQYGLLIFGAAVSVLLQEVFRFAYYKLLKKADEGLASLSEDGRSPISIRQMAYVSGLSFGIISGVFSVINILADALGPGVVGIHGDSPYYFLTSAFLTAAIILLHTFWGVVFFDACERRRYWALGLVVGSHLLTSGLTFLNPWYEASLLPIYAVTVSMGLWAFITAGGSLRSIQRSLLCRRQEDSRVMVYSALRIPPED
  
Component 2
Name:
Gamma-secretase subunit PEN-2
Synonyms:
Gamma-Secretase Subunit PEN-2 | Gamma-secretase | PEN2 | PEN2_HUMAN | PSENEN | Presenilin enhancer protein 2
Type:
Enzyme subunit; multi-pass membrane protein
Mol. Mass.:
12031.98
Organism:
Homo sapiens (Human)
Description:
n/a
Residue:
101
Sequence:
MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP
  
Component 3
Name:
Nicastrin [34-709]
Synonyms:
Gamma-Secretase Subunit Nicastrin | KIAA0253 | NCSTN | NICA_HUMAN
Type:
Single-pass type I membrane protein
Mol. Mass.:
75243.23
Organism:
Homo sapiens (Human)
Description:
Q92542[34-709]
Residue:
676
Sequence:
NSVERKIYIPLNKTAPCVRLLNATHQIGCQSSISGDTGVIHVVEKEEDLQWVLTDGPNPPYMVLLESKHFTRDLMEKLKGRTSRIAGLAVSLTKPSPASGFSPSVQCPNDGFGVYSNSYGPEFAHCREIQWNSLGNGLAYEDFSFPIFLLEDENETKVIKQCYQDHNLSQNGSAPTFPLCAMQLFSHMHAVISTATCMRRSSIQSTFSINPEIVCDPLSDYNVWSMLKPINTTGTLKPDDRVVVAATRLDSRSFFWNVAPGAESAVASFVTQLAAAEALQKAPDVTTLPRNVMFVFFQGETFDYIGSSRMVYDMEKGKFPVQLENVDSFVELGQVALRTSLELWMHTDPVSQKNESVRNQVEDLLATLEKSGAGVPAVILRRPNQSQPLPPSSLQRFLRARNISGVVLADHSGAFHNKYYQSIYDTAENINVSYPEWLSPEEDLNFVTDTAKALADVATVLGRALYELAGGTNFSDTVQADPQTVTRLLYGFLIKANNSWFQSILRQDLRSYLGDGPLQHYIAVSSPTNTTYVVQYALANLTGTVVNLTREQCQDPSKVPSENKDLYEYSWVQGPLHSNETDRLPRCVRSTARLARALSPAFELSQWSSTEYSTWTESRWKDIRARIFLIASKELELITLTVGFGILIFSLIVTYCINAKADVLFIAPREPGAVSY
  
Component 4
Name:
Presenilin-1
Synonyms:
3.4.23.- | AD3 | Gamma-Secretase Subunit Presenilin-1 | PS-1 | PS1 | PS1-CTF12 | PSEN1 | PSN1_HUMAN | PSNL1 | Presenilin-1 CTF subunit | Presenilin-1 CTF12 | Presenilin-1 NTF subunit | Protein S182
Type:
n/a
Mol. Mass.:
52657.13
Organism:
Homo sapiens (Human)
Description:
P49768
Residue:
467
Sequence:
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSRQVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTEDTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFIYLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKYLPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAEGDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAAVQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCLTLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
  
Inhibitor
Name:
BDBM28998
Synonyms:
(2R)-2-{[5-chloro-2-(hydroxymethyl)phenyl](4-chlorobenzene)sulfonamido}propyl N-tert-butylcarbamate | Carbamate-appended N-alkylsulfonamide, 20
Type:
Small organic molecule
Emp. Form.:
C21H26Cl2N2O5S
Mol. Mass.:
489.413
SMILES:
C[C@H](COC(=O)NC(C)(C)C)N(c1cc(Cl)ccc1CO)S(=O)(=O)c1ccc(Cl)cc1 |r|
Structure:
Search PDB for entries with ligand similarity:
Substrate
Name:
Amyloid-beta precursor protein
Synonyms:
A4 | A4_HUMAN | ABPP | AD1 | AICD-50 | AICD-57 | AICD-59 | AID(50) | AID(57) | AID(59) | APP | APPI | Alzheimer disease amyloid protein | Amyloid beta A4 protein | Amyloid beta Protein | Amyloid beta protein (sAPPbeta) | Amyloid beta protein Abeta(1-42) | Amyloid intracellular domain 50 | Amyloid intracellular domain 57 | Amyloid intracellular domain 59 | Amyloid protein (Abeta42b) | Amyloid β-protein (Aβ42) | Beta amyloid A4 protein | Beta-APP40 | Beta-APP42 | Beta-amyloid protein 40 | Beta-amyloid protein 42 | C31 | C83 | C99 | CVAP | Cerebral vascular amyloid peptide | Gamma Secretase | Gamma-CTF(50) | Gamma-CTF(57) | Gamma-CTF(59) | Gamma-secretase | Gamma-secretase C-terminal fragment 50 | Gamma-secretase C-terminal fragment 57 | Gamma-secretase C-terminal fragment 59 | P3(40) | P3(42) | PN-II | PreA4 | Protease nexin-II | S-APP-alpha | S-APP-beta | Soluble APP-alpha | Soluble APP-beta | beta-Amyloid Precursor Protein (APP)
Type:
Single-pass type I membrane protein
Mol. Mass.:
86890.41
Organism:
Homo sapiens (Human)
Description:
P05067
Residue:
770
Sequence:
MLPGLALLLLAAWTARALEVPTDGNAGLLAEPQIAMFCGRLNMHMNVQNGKWDSDPSGTKTCIDTKEGILQYCQEVYPELQITNVVEANQPVTIQNWCKRGRKQCKTHPHFVIPYRCLVGEFVSDALLVPDKCKFLHQERMDVCETHLHWHTVAKETCSEKSTNLHDYGMLLPCGIDKFRGVEFVCCPLAEESDNVDSADAEEDDSDVWWGGADTDYADGSEDKVVEVAEEEEVAEVEEEEADDDEDDEDGDEVEEEAEEPYEEATERTTSIATTTTTTTESVEEVVREVCSEQAETGPCRAMISRWYFDVTEGKCAPFFYGGCGGNRNNFDTEEYCMAVCGSAMSQSLLKTTQEPLARDPVKLPTTAASTPDAVDKYLETPGDENEHAHFQKAKERLEAKHRERMSQVMREWEEAERQAKNLPKADKKAVIQHFQEKVESLEQEAANERQQLVETHMARVEAMLNDRRRLALENYITALQAVPPRPRHVFNMLKKYVRAEQKDRQHTLKHFEHVRMVDPKKAAQIRSQVMTHLRVIYERMNQSLSLLYNVPAVAEEIQDEVDELLQKEQNYSDDVLANMISEPRISYGNDALMPSLTETKTTVELLPVNGEFSLDDLQPWHSFGADSVPANTENEVEPVDARPAADRGLTTRPGSGLTNIKTEEISEVKMDAEFRHDSGYEVHHQKLVFFAEDVGSNKGAIIGLMVGGVVIATVIVITLVMLKKKQYTSIHHGVVEVDAAVTPEERHLSKMQQNGYENPTYKFFEQMQN