Structure of PDB 4h3i Chain A Binding Site BS01

Receptor Information
>4h3i Chain A (length=387) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPGKWEGELGTDLVSIPHGPNVTVRANI
AAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPNL
FSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYY
EVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIK
AASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRIT
ILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRAR
KRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNI
Ligand information
Ligand ID10V
InChIInChI=1S/C24H22N6O2S/c1-29-22(31)18-12-30(21-19(32-2)7-4-8-27-21)14-24(18,28-23(29)26)20-10-17(13-33-20)16-6-3-5-15(9-16)11-25/h3-10,13,18H,12,14H2,1-2H3,(H2,26,28)/t18-,24-/m0/s1
InChIKeyOVZBZLASXPSCEA-UUOWRZLLSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6[H]/N=C/1\N[C@]2(CN(C[C@H]2C(=O)N1C)c3c(cccn3)OC)c4cc(cs4)c5cccc(c5)C#N
CACTVS 3.370COc1cccnc1N2C[C@H]3C(=O)N(C)C(=N)N[C@]3(C2)c4scc(c4)c5cccc(c5)C#N
OpenEye OEToolkits 1.7.6CN1C(=O)C2CN(CC2(NC1=N)c3cc(cs3)c4cccc(c4)C#N)c5c(cccn5)OC
ACDLabs 12.01O=C4N(C(=[N@H])NC5(c2scc(c1cc(C#N)ccc1)c2)CN(c3ncccc3OC)CC45)C
CACTVS 3.370COc1cccnc1N2C[CH]3C(=O)N(C)C(=N)N[C]3(C2)c4scc(c4)c5cccc(c5)C#N
FormulaC24 H22 N6 O2 S
Name3-{5-[(2E,4aR,7aR)-2-imino-6-(3-methoxypyridin-2-yl)-3-methyl-4-oxooctahydro-7aH-pyrrolo[3,4-d]pyrimidin-7a-yl]thiophen-3-yl}benzonitrile
ChEMBLCHEMBL2178712
DrugBank
ZINCZINC000034787864
PDB chain4h3i Chain A Residue 502 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4h3i Design and Validation of Bicyclic Iminopyrimidinones As Beta Amyloid Cleaving Enzyme-1 (BACE1) Inhibitors: Conformational Constraint to Favor a Bioactive Conformation.
Resolution1.96 Å
Binding residue
(original residue number in PDB)		Q73 L91 D93 S96 V130 F169 W176 D289 G291
Binding residue
(residue number reindexed from 1)		Q16 L34 D36 S39 V73 F109 W116 D229 G231
Annotation score1
Binding affinityMOAD: Ki=3nM
PDBbind-CN: -logKd/Ki=8.52,Ki=3nM
Enzymatic activity
Catalytic site (original residue number in PDB) D93 S96 N98 A100 D289 T292
Catalytic site (residue number reindexed from 1) D36 S39 N41 A43 D229 T232
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:4h3i, PDBe:4h3i, PDBj:4h3i
PDBsum4h3i
PubMed22989333
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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