Structure of PDB 4i12 Chain A Binding Site BS01

Receptor Information
>4i12 Chain A (length=374) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
MVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHRY
YQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRANIAA
ITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPNLFS
LQLCGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQDLKMD
CKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDGFWLGEQ
LVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVTSQDDCY
KFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVRTAAVEGPF
VTLDMEDCGYNIPQTDESRSHHHH
Ligand information
Ligand ID1BC
InChIInChI=1S/C27H29ClN6OS/c1-4-5-23-20(21(15-36-23)17-13-30-31-14-17)11-22(26-29-9-8-24(35)33-26)32-25-19-7-6-18(28)10-16(19)12-27(2,3)34-25/h6-7,9-10,13-15,22H,4-5,8,11-12H2,1-3H3,(H,30,31)(H,32,34)/t22-/m0/s1
InChIKeySHQGADSMADPNBQ-QFIPXVFZSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CCCc1c(c(cs1)c2c[nH]nc2)C[C@@H](C3=NC(=O)CC=N3)/N=C\4/c5ccc(cc5CC(N4)(C)C)Cl
CACTVS 3.370CCCc1scc(c1C[CH](N=C2NC(C)(C)Cc3cc(Cl)ccc23)C4=NC(=O)CC=N4)c5c[nH]nc5
CACTVS 3.370CCCc1scc(c1C[C@H](N=C2NC(C)(C)Cc3cc(Cl)ccc23)C4=NC(=O)CC=N4)c5c[nH]nc5
OpenEye OEToolkits 1.7.6CCCc1c(c(cs1)c2c[nH]nc2)CC(C3=NC(=O)CC=N3)N=C4c5ccc(cc5CC(N4)(C)C)Cl
ACDLabs 12.01O=C1N=C(N=CC1)C(/N=C3/c2ccc(Cl)cc2CC(N3)(C)C)Cc5c(scc5c4cnnc4)CCC
FormulaC27 H29 Cl N6 O S
Name2-{(1S)-1-{[(1Z)-6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1(2H)-ylidene]amino}-2-[2-propyl-4-(1H-pyrazol-4-yl)thiophen-3-yl]ethyl}pyrimidin-4(5H)-one
ChEMBL
DrugBank
ZINCZINC000098207938
PDB chain4i12 Chain A Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4i12 Design and synthesis of thiophene dihydroisoquinolines as novel BACE1 inhibitors.
Resolution1.78 Å
Binding residue
(original residue number in PDB)		Q73 G74 Y132 G135 K136 K168 F169 I171 W176 G291 T292 T293 N294
Binding residue
(residue number reindexed from 1)		Q11 G12 Y70 G73 K74 K106 F107 I109 W114 G214 T215 T216 N217
Annotation score1
Binding affinityMOAD: ic50=40uM
PDBbind-CN: -logKd/Ki=6.39,IC50=0.406uM
Enzymatic activity
Catalytic site (original residue number in PDB) D93 S96 N98 A100 Y132 D289 T292
Catalytic site (residue number reindexed from 1) D31 S34 N36 A38 Y70 D212 T215
Enzyme Commision number 3.4.23.46: memapsin 2.
Gene Ontology
Molecular Function
GO:0004190 aspartic-type endopeptidase activity
Biological Process
GO:0006508 proteolysis
Cellular Component
GO:0016020 membrane

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4i12, PDBe:4i12, PDBj:4i12
PDBsum4i12
PubMed23570791
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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