Structure of PDB 4d83 Chain B Binding Site BS01

Receptor Information
>4d83 Chain B (length=377) 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
VEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSA
CHVHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID0GT
InChIInChI=1S/C27H34F2N2O3S/c1-27(2,3)21-6-4-5-18(10-21)13-30-24-16-35(33,34)15-20(26(24)32)9-17-7-8-23-22(11-17)19(14-31-23)12-25(28)29/h4-8,10-11,14,20,24-26,30-32H,9,12-13,15-16H2,1-3H3/t20-,24+,26+/m1/s1
InChIKeyOOZZVYSXZBAROL-PSUQPPDWSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C)(C)c1cccc(c1)CNC2CS(=O)(=O)CC(C2O)Cc3ccc4c(c3)c(c[nH]4)CC(F)F
CACTVS 3.370CC(C)(C)c1cccc(CN[C@H]2C[S](=O)(=O)C[C@@H](Cc3ccc4[nH]cc(CC(F)F)c4c3)[C@@H]2O)c1
CACTVS 3.370CC(C)(C)c1cccc(CN[CH]2C[S](=O)(=O)C[CH](Cc3ccc4[nH]cc(CC(F)F)c4c3)[CH]2O)c1
ACDLabs 12.01O=S2(=O)CC(C(O)C(NCc1cccc(c1)C(C)(C)C)C2)Cc4ccc3ncc(c3c4)CC(F)F
OpenEye OEToolkits 1.7.6CC(C)(C)c1cccc(c1)CN[C@H]2CS(=O)(=O)C[C@H]([C@@H]2O)Cc3ccc4c(c3)c(c[nH]4)CC(F)F
FormulaC27 H34 F2 N2 O3 S
Name(3R,4S,5S)-3-[(3-tert-butylbenzyl)amino]-5-{[3-(2,2-difluoroethyl)-1H-indol-5-yl]methyl}tetrahydro-2H-thiopyran-4-ol 1,1-dioxide
ChEMBLCHEMBL2047898
DrugBank
ZINCZINC000084653228
PDB chain4d83 Chain B Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4d83 Discovery of cyclic sulfone hydroxyethylamines as potent and selective beta-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure based design and in vivo reduction of amyloid beta-peptides
Resolution2.4 Å
Binding residue
(original residue number in PDB)		G13 L30 D32 G34 S35 P70 Y71 T72 F108 I110 W115 Y187 D217 G219 T220 R224
Binding residue
(residue number reindexed from 1)		G16 L33 D35 G37 S38 P73 Y74 T75 F111 I113 W118 Y190 D220 G222 T223 R227
Annotation score1
Binding affinityMOAD: ic50=0.055uM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D217 T220
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:4d83, PDBe:4d83, PDBj:4d83
PDBsum4d83
PubMed22380629
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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