Structure of PDB 4d88 Chain A Binding Site BS01

Receptor Information
>4d88 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]
SFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPF
LHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRA
NIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVP
NLFSLQLCGAGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEING
QDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDG
FWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVE
DVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACH
VHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand IDBXQ
InChIInChI=1S/C26H34F4N2O4S/c1-25(2,3)19-6-4-5-15(9-19)12-32-21-14-37(35,36)13-18(24(21)34)8-16-7-17(23(31)20(27)10-16)11-22(33)26(28,29)30/h4-7,9-10,18,21-22,24,32-34H,8,11-14,31H2,1-3H3/t18-,21+,22+,24+/m1/s1
InChIKeyGCVKLIOGBJALOK-VPJOFFEXSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C)(C)c1cccc(c1)CN[C@H]2CS(=O)(=O)C[C@H]([C@@H]2O)Cc3cc(c(c(c3)F)N)C[C@@H](C(F)(F)F)O
CACTVS 3.370CC(C)(C)c1cccc(CN[CH]2C[S](=O)(=O)C[CH](Cc3cc(F)c(N)c(C[CH](O)C(F)(F)F)c3)[CH]2O)c1
CACTVS 3.370CC(C)(C)c1cccc(CN[C@H]2C[S](=O)(=O)C[C@@H](Cc3cc(F)c(N)c(C[C@H](O)C(F)(F)F)c3)[C@@H]2O)c1
OpenEye OEToolkits 1.7.6CC(C)(C)c1cccc(c1)CNC2CS(=O)(=O)CC(C2O)Cc3cc(c(c(c3)F)N)CC(C(F)(F)F)O
ACDLabs 12.01O=S2(=O)CC(C(O)C(NCc1cccc(c1)C(C)(C)C)C2)Cc3cc(c(N)c(F)c3)CC(O)C(F)(F)F
FormulaC26 H34 F4 N2 O4 S
Name(3S,4S,5R)-3-{4-amino-3-fluoro-5-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]benzyl}-5-[(3-tert-butylbenzyl)amino]tetrahydro-2H-thiopyran-4-ol 1,1-dioxide
ChEMBLCHEMBL2047912
DrugBank
ZINCZINC000084653847
PDB chain4d88 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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PDB4d88 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
Resolution1.7 Å
Binding residue
(original residue number in PDB)		G11 Q12 G13 D32 G34 S35 Y71 T72 F108 I110 Y185 D215 G217 T218
Binding residue
(residue number reindexed from 1)		G14 Q15 G16 D35 G37 S38 Y74 T75 F111 I113 Y188 D218 G220 T221
Annotation score1
Binding affinityMOAD: ic50=0.049uM
PDBbind-CN: -logKd/Ki=7.31,IC50=0.049uM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D215 T218
Catalytic site (residue number reindexed from 1) D35 S38 N40 A42 Y74 D218 T221
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:4d88, PDBe:4d88, PDBj:4d88
PDBsum4d88
PubMed22380629
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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