Structure of PDB 4ke0 Chain C Binding Site BS01

Receptor Information
>4ke0 Chain C (length=372) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPF
LHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRA
NIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVP
NLFSLQLCGASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEI
NGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFP
DGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRP
VEDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDE
FRTAAVEGPFVTLDMEDCGYNI
Ligand information
Ligand ID1R8
InChIInChI=1S/C31H42N2O3/c1-2-22-13-14-29-25(18-22)27(20-31(36-29)15-8-16-31)32-21-28(34)26-19-24-11-7-10-23(17-24)9-5-3-4-6-12-30(35)33-26/h7,10-11,13-14,17-18,26-28,32,34H,2-6,8-9,12,15-16,19-21H2,1H3,(H,33,35)/t26-,27-,28+/m0/s1
InChIKeyNUISAGYICVEVAE-HZFUHODCSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CCc1ccc2c(c1)C(CC3(O2)CCC3)NCC(C4Cc5cccc(c5)CCCCCCC(=O)N4)O
CACTVS 3.370CCc1ccc2OC3(CCC3)C[CH](NC[CH](O)[CH]4Cc5cccc(CCCCCCC(=O)N4)c5)c2c1
ACDLabs 12.01O=C2NC(Cc1cccc(c1)CCCCCC2)C(O)CNC3c5c(OC4(C3)CCC4)ccc(c5)CC
OpenEye OEToolkits 1.7.6CCc1ccc2c(c1)[C@H](CC3(O2)CCC3)NC[C@H]([C@@H]4Cc5cccc(c5)CCCCCCC(=O)N4)O
CACTVS 3.370CCc1ccc2OC3(CCC3)C[C@H](NC[C@@H](O)[C@@H]4Cc5cccc(CCCCCCC(=O)N4)c5)c2c1
FormulaC31 H42 N2 O3
Name(3S)-3-[(1R)-2-{[(4S)-6-ethyl-3,4-dihydrospiro[chromene-2,1'-cyclobutan]-4-yl]amino}-1-hydroxyethyl]-4-azabicyclo[10.3.1]hexadeca-1(16),12,14-trien-5-one
ChEMBLCHEMBL2407344
DrugBank
ZINCZINC000095921203
PDB chain4ke0 Chain C Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4ke0 Hydroxyethylamine-based inhibitors of BACE1: P1-P3 macrocyclization can improve potency, selectivity, and cell activity.
Resolution2.3 Å
Binding residue
(original residue number in PDB)		L30 D32 G34 P70 Y71 T72 F108 W115 I118 Y198 D228 G230 T329 V332
Binding residue
(residue number reindexed from 1)		L33 D35 G37 P73 Y74 T75 F111 W118 I121 Y190 D220 G222 T315 V318
Annotation score1
Binding affinityMOAD: ic50=0.017uM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
Catalytic site (residue number reindexed from 1) D35 S38 N40 A42 Y74 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:4ke0, PDBe:4ke0, PDBj:4ke0
PDBsum4ke0
PubMed23769639
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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