Structure of PDB 4ke1 Chain A Binding Site BS01

Receptor Information
>4ke1 Chain A (length=355) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGAASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEI
NGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFP
DGFWTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVYKFAISQSSTG
TVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDEFRTAAVEGPFVTLDME
DCGYN
Ligand information
Ligand ID1R6
InChIInChI=1S/C34H41N3O4/c1-2-23-10-12-31-27(18-23)29(20-34(41-31)14-6-15-34)35-21-30(38)28-19-25-9-5-8-24(17-25)7-3-4-16-37-22-26(33(40)36-28)11-13-32(37)39/h5,8-13,17-18,22,28-30,35,38H,2-4,6-7,14-16,19-21H2,1H3,(H,36,40)/t28-,29-,30+/m0/s1
InChIKeyLCSGKLXXIKDHLA-OIFRRMEBSA-N
SMILES
SoftwareSMILES
CACTVS 3.370CCc1ccc2OC3(CCC3)C[CH](NC[CH](O)[CH]4Cc5cccc(CCCC[N]6C=C(C=CC6=O)C(=O)N4)c5)c2c1
ACDLabs 12.01O=C1C=CC3=CN1CCCCc2cccc(c2)CC(NC3=O)C(O)CNC4c6c(OC5(C4)CCC5)ccc(c6)CC
CACTVS 3.370CCc1ccc2OC3(CCC3)C[C@H](NC[C@@H](O)[C@@H]4Cc5cccc(CCCC[N@@]6C=C(C=CC6=O)C(=O)N4)c5)c2c1
OpenEye OEToolkits 1.7.6CCc1ccc2c(c1)C(CC3(O2)CCC3)NCC(C4Cc5cccc(c5)CCCCN6C=C(C=CC6=O)C(=O)N4)O
OpenEye OEToolkits 1.7.6CCc1ccc2c(c1)[C@H](CC3(O2)CCC3)NC[C@H]([C@@H]4Cc5cccc(c5)CCCCN6C=C(C=CC6=O)C(=O)N4)O
FormulaC34 H41 N3 O4
Name(12S)-12-[(1R)-2-{[(4S)-6-ethyl-3,4-dihydrospiro[chromene-2,1'-cyclobutan]-4-yl]amino}-1-hydroxyethyl]-1,13-diazatricyclo[13.3.1.1~6,10~]icosa-6(20),7,9,15(19),16-pentaene-14,18-dione
ChEMBLCHEMBL2407488
DrugBank
ZINCZINC000096273403
PDB chain4ke1 Chain A Residue 404 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4ke1 Hydroxyethylamine-based inhibitors of BACE1: P1-P3 macrocyclization can improve potency, selectivity, and cell activity.
Resolution1.91 Å
Binding residue
(original residue number in PDB)		Q12 L30 D32 G34 S35 Y71 T72 F108 Y198 D228 G230 T329
Binding residue
(residue number reindexed from 1)		Q14 L32 D34 G36 S37 Y73 T74 F110 Y190 D220 G222 T299
Annotation score1
Binding affinityMOAD: ic50=0.0025uM
PDBbind-CN: -logKd/Ki=8.60,IC50=2.5nM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
Catalytic site (residue number reindexed from 1) D34 S37 N39 A41 Y73 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:4ke1, PDBe:4ke1, PDBj:4ke1
PDBsum4ke1
PubMed23769639
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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