Structure of PDB 4d8c Chain A Binding Site BS01

Receptor Information
>4d8c Chain A (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 IDBXD
InChIInChI=1S/C28H38F4N2O5S/c1-5-38-14-24(28(30,31)32)39-23-12-18(11-21(29)25(23)33)9-19-15-40(36,37)16-22(26(19)35)34-13-17-7-6-8-20(10-17)27(2,3)4/h6-8,10-12,19,22,24,26,34-35H,5,9,13-16,33H2,1-4H3/t19-,22+,24-,26+/m1/s1
InChIKeyUJZFSYZNJMWXJO-NJONLQHESA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CCOCC(C(F)(F)F)Oc1cc(cc(c1N)F)CC2CS(=O)(=O)CC(C2O)NCc3cccc(c3)C(C)(C)C
OpenEye OEToolkits 1.7.6CCOC[C@H](C(F)(F)F)Oc1cc(cc(c1N)F)C[C@@H]2CS(=O)(=O)C[C@@H]([C@H]2O)NCc3cccc(c3)C(C)(C)C
ACDLabs 12.01O=S2(=O)CC(C(O)C(NCc1cccc(c1)C(C)(C)C)C2)Cc3cc(F)c(N)c(OC(C(F)(F)F)COCC)c3
CACTVS 3.370CCOC[CH](Oc1cc(C[CH]2C[S](=O)(=O)C[CH](NCc3cccc(c3)C(C)(C)C)[CH]2O)cc(F)c1N)C(F)(F)F
CACTVS 3.370CCOC[C@@H](Oc1cc(C[C@@H]2C[S](=O)(=O)C[C@H](NCc3cccc(c3)C(C)(C)C)[C@H]2O)cc(F)c1N)C(F)(F)F
FormulaC28 H38 F4 N2 O5 S
Name(3S,4S,5R)-3-(4-amino-3-{[(2R)-3-ethoxy-1,1,1-trifluoropropan-2-yl]oxy}-5-fluorobenzyl)-5-[(3-tert-butylbenzyl)amino]tetrahydro-2H-thiopyran-4-ol 1,1-dioxide
ChEMBLCHEMBL2048051
DrugBank
ZINCZINC000084669160
PDB chain4d8c 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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PDB4d8c 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
Resolution2.07 Å
Binding residue
(original residue number in PDB)		Q12 G13 L30 D32 G34 S35 Y71 T72 Q73 F108 I110 Y187 D217 G219 T220
Binding residue
(residue number reindexed from 1)		Q15 G16 L33 D35 G37 S38 Y74 T75 Q76 F111 I113 Y190 D220 G222 T223
Annotation score1
Binding affinityMOAD: ic50=0.002uM
PDBbind-CN: -logKd/Ki=8.70,IC50=2nM
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:4d8c, PDBe:4d8c, PDBj:4d8c
PDBsum4d8c
PubMed22380629
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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