Structure of PDB 4d85 Chain A Binding Site BS01

Receptor Information
>4d85 Chain A (length=374) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGAASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVEDDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHV
HDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID0GU
InChIInChI=1S/C30H39F3N2O3S/c1-28(2,3)22-6-4-5-19(12-22)15-34-25-17-39(37,38)16-21(27(25)36)11-20-13-23-26(24(31)14-20)35-18-29(23)7-9-30(32,33)10-8-29/h4-6,12-14,21,25,27,34-36H,7-11,15-18H2,1-3H3/t21-,25+,27+/m1/s1
InChIKeyYSVPVGYQIWTLEZ-UDZXTKBFSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C)(C)c1cccc(c1)CN[C@H]2CS(=O)(=O)C[C@H]([C@@H]2O)Cc3cc4c(c(c3)F)NCC45CCC(CC5)(F)F
ACDLabs 12.01O=S2(=O)CC(C(O)C(NCc1cccc(c1)C(C)(C)C)C2)Cc5cc3c(NCC34CCC(F)(F)CC4)c(F)c5
OpenEye OEToolkits 1.7.6CC(C)(C)c1cccc(c1)CNC2CS(=O)(=O)CC(C2O)Cc3cc4c(c(c3)F)NCC45CCC(CC5)(F)F
CACTVS 3.370CC(C)(C)c1cccc(CN[CH]2C[S](=O)(=O)C[CH](Cc3cc(F)c4NCC5(CCC(F)(F)CC5)c4c3)[CH]2O)c1
CACTVS 3.370CC(C)(C)c1cccc(CN[C@H]2C[S](=O)(=O)C[C@@H](Cc3cc(F)c4NCC5(CCC(F)(F)CC5)c4c3)[C@@H]2O)c1
FormulaC30 H39 F3 N2 O3 S
Name(3R,4S,5S)-3-[(3-tert-butylbenzyl)amino]-5-[(4,4,7'-trifluoro-1',2'-dihydrospiro[cyclohexane-1,3'-indol]-5'-yl)methyl]tetrahydro-2H-thiopyran-4-ol 1,1-dioxide
ChEMBLCHEMBL2047901
DrugBank
ZINCZINC000084654025
PDB chain4d85 Chain A Residue 401 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4d85 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
Resolution2.65 Å
Binding residue
(original residue number in PDB)		G13 D34 G36 S37 Y73 T74 Q75 G76 F110 I112 R130 Y190 D220 G222
Binding residue
(residue number reindexed from 1)		G15 D36 G38 S39 Y75 T76 Q77 G78 F112 I114 R132 Y192 D222 G224
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=6.85,IC50=0.14uM
Enzymatic activity
Catalytic site (original residue number in PDB) D34 S37 N39 A41 Y73 D220 T223
Catalytic site (residue number reindexed from 1) D36 S39 N41 A43 Y75 D222 T225
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:4d85, PDBe:4d85, PDBj:4d85
PDBsum4d85
PubMed22380629
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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