Structure of PDB 4dh6 Chain A Binding Site BS01

Receptor Information
>4dh6 Chain A (length=367) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEIN
GQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPD
GFWLGEQLVCWQATPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVDD
CYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDEFRTA
AVEGPFVTLDMEDCGYN
Ligand information
Ligand ID0KN
InChIInChI=1S/C31H43N3O6/c1-19(37-5)28(36)34-23(12-20-7-8-26-27(13-20)39-18-38-26)25(35)17-32-24-15-31(9-6-10-31)40-29-22(24)11-21(16-33-29)14-30(2,3)4/h7-8,11,13,16,19,23-25,32,35H,6,9-10,12,14-15,17-18H2,1-5H3,(H,34,36)/t19-,23+,24+,25-/m1/s1
InChIKeyOMMVFRZSBCRMQD-LJYZBVLISA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C(=O)NC(Cc1ccc2c(c1)OCO2)C(CNC3CC4(CCC4)Oc5c3cc(cn5)CC(C)(C)C)O)OC
OpenEye OEToolkits 1.7.6C[C@H](C(=O)N[C@@H](Cc1ccc2c(c1)OCO2)[C@@H](CN[C@H]3CC4(CCC4)Oc5c3cc(cn5)CC(C)(C)C)O)OC
CACTVS 3.370CO[C@H](C)C(=O)N[C@@H](Cc1ccc2OCOc2c1)[C@H](O)CN[C@H]3CC4(CCC4)Oc5ncc(CC(C)(C)C)cc35
ACDLabs 12.01O=C(NC(Cc2ccc1OCOc1c2)C(O)CNC4c3c(ncc(c3)CC(C)(C)C)OC5(C4)CCC5)C(OC)C
CACTVS 3.370CO[CH](C)C(=O)N[CH](Cc1ccc2OCOc2c1)[CH](O)CN[CH]3CC4(CCC4)Oc5ncc(CC(C)(C)C)cc35
FormulaC31 H43 N3 O6
Name(2R)-N-[(2S,3R)-1-(1,3-benzodioxol-5-yl)-4-{[(4'S)-6'-(2,2-dimethylpropyl)-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridin]-4'-yl]amino}-3-hydroxybutan-2-yl]-2-methoxypropanamide;
(2R)-N-((2S,3R)-1-(benzo[d][1,3]dioxol-5-yl)-3-hydroxy-4-((S)-6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridine]-4'-ylamino)butan-2-yl)-2-methoxypropanamide
ChEMBLCHEMBL2181880
DrugBank
ZINCZINC000095572350
PDB chain4dh6 Chain A Residue 411 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4dh6 Design and preparation of a potent series of hydroxyethylamine containing beta-secretase inhibitors that demonstrate robust reduction of central beta-amyloid.
Resolution2.5 Å
Binding residue
(original residue number in PDB)		L30 D32 G34 P70 Y71 T72 F108 W115 D228 G230 T329 V332
Binding residue
(residue number reindexed from 1)		L32 D34 G36 P72 Y73 T74 F110 W117 D219 G221 T311 V314
Annotation score1
Binding affinityMOAD: ic50=16.8nM
PDBbind-CN: -logKd/Ki=7.77,IC50=16.8nM
BindingDB: IC50=26nM
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 D219 T222
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:4dh6, PDBe:4dh6, PDBj:4dh6
PDBsum4dh6
PubMed22468639
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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