Structure of PDB 4ke0 Chain A Binding Site BS01

Receptor Information
>4ke0 Chain A (length=375) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPH
PFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTV
RANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTH
VPNLFSLQLCGAASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVR
VEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTE
KFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQY
LRPVEDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHV
HDEFRTAAVEGPFVTLDMEDCGYNI
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 A Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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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)		D32 G34 P70 Y71 T72 F108 I110 W115 Y198 K224 D228 G230 T329
Binding residue
(residue number reindexed from 1)		D37 G39 P75 Y76 T77 F113 I115 W120 Y193 K219 D223 G225 T318
Annotation score1
Binding affinityMOAD: ic50=0.017uM
PDBbind-CN: -logKd/Ki=7.77,IC50=17nM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
Catalytic site (residue number reindexed from 1) D37 S40 N42 A44 Y76 D223 T226
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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