Structure of PDB 4exg Chain A Binding Site BS01

Receptor Information
>4exg Chain A (length=377) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
VEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLH
RYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRANI
AAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPNL
FSLQLCGAGASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEI
NGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFP
DGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRP
VEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSA
CHVHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID916
InChIInChI=1S/C26H38N2O3S/c1-17(29)28-21(12-18-10-8-7-9-11-18)23(30)16-27-22-15-26(5,6)31-24-20(22)13-19(32-24)14-25(2,3)4/h7-11,13,21-23,27,30H,12,14-16H2,1-6H3,(H,28,29)/t21-,22-,23+/m0/s1
InChIKeyYLIBYDKWVPKMKX-RJGXRXQPSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01O=C(NC(Cc1ccccc1)C(O)CNC2c3cc(sc3OC(C2)(C)C)CC(C)(C)C)C
OpenEye OEToolkits 1.7.6CC(=O)N[C@@H](Cc1ccccc1)[C@@H](CN[C@H]2CC(Oc3c2cc(s3)CC(C)(C)C)(C)C)O
OpenEye OEToolkits 1.7.6CC(=O)NC(Cc1ccccc1)C(CNC2CC(Oc3c2cc(s3)CC(C)(C)C)(C)C)O
CACTVS 3.370CC(=O)N[CH](Cc1ccccc1)[CH](O)CN[CH]2CC(C)(C)Oc3sc(CC(C)(C)C)cc23
CACTVS 3.370CC(=O)N[C@@H](Cc1ccccc1)[C@H](O)CN[C@H]2CC(C)(C)Oc3sc(CC(C)(C)C)cc23
FormulaC26 H38 N2 O3 S
NameN-[(2S,3R)-4-{[(4S)-6-(2,2-dimethylpropyl)-2,2-dimethyl-3,4-dihydro-2H-thieno[2,3-b]pyran-4-yl]amino}-3-hydroxy-1-phenylbutan-2-yl]acetamide
ChEMBL
DrugBank
ZINCZINC000095574915
PDB chain4exg Chain A Residue 500 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4exg Design and synthesis of potent hydroxyethylamine (HEA) BACE-1 inhibitors carrying prime side 4,5,6,7-tetrahydrobenzazole and 4,5,6,7-tetrahydropyridinoazole templates.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		L78 D80 G82 Y119 T120 F156 W163 Y246 D276 G278
Binding residue
(residue number reindexed from 1)		L31 D33 G35 Y72 T73 F109 W116 Y190 D220 G222
Annotation score1
Binding affinityMOAD: ic50=8.5nM
PDBbind-CN: -logKd/Ki=8.07,IC50=8.5nM
Enzymatic activity
Catalytic site (original residue number in PDB) D80 S83 N85 A87 Y119 D276 T279
Catalytic site (residue number reindexed from 1) D33 S36 N38 A40 Y72 D220 T223
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:4exg, PDBe:4exg, PDBj:4exg
PDBsum4exg
PubMed23010268
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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