Structure of PDB 4lxm Chain A Binding Site BS01

Receptor Information
>4lxm 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 ID1YU
InChIInChI=1S/C26H31F7N2O3S/c1-24(2,3)17-6-4-5-14(8-17)11-35-19-13-39(37)12-16(22(19)36)7-15-9-18(27)21(34)20(10-15)38-23(25(28,29)30)26(31,32)33/h4-6,8-10,16,19,22-23,35-36H,7,11-13,34H2,1-3H3/t16-,19+,22+,39+/m1/s1
InChIKeySVZBUJIOBQPGEC-DAMLKHMOSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CC(C)(C)c1cccc(CN[C@H]2C[S@@](=O)C[C@@H](Cc3cc(F)c(N)c(OC(C(F)(F)F)C(F)(F)F)c3)[C@@H]2O)c1
ACDLabs 12.01O=S2CC(C(O)C(NCc1cccc(c1)C(C)(C)C)C2)Cc3cc(F)c(N)c(OC(C(F)(F)F)C(F)(F)F)c3
CACTVS 3.385CC(C)(C)c1cccc(CN[CH]2C[S](=O)C[CH](Cc3cc(F)c(N)c(OC(C(F)(F)F)C(F)(F)F)c3)[CH]2O)c1
OpenEye OEToolkits 1.7.6CC(C)(C)c1cccc(c1)CNC2CS(=O)CC(C2O)Cc3cc(c(c(c3)F)N)OC(C(F)(F)F)C(F)(F)F
OpenEye OEToolkits 1.7.6CC(C)(C)c1cccc(c1)CN[C@H]2C[S@@](=O)C[C@H]([C@@H]2O)Cc3cc(c(c(c3)F)N)OC(C(F)(F)F)C(F)(F)F
FormulaC26 H31 F7 N2 O3 S
Name(1S,3S,4S,5R)-3-{4-amino-3-fluoro-5-[(1,1,1,3,3,3-hexafluoropropan-2-yl)oxy]benzyl}-5-[(3-tert-butylbenzyl)amino]tetrahydro-2H-thiopyran-4-ol 1-oxide
ChEMBLCHEMBL2425609
DrugBank
ZINCZINC000059049521
PDB chain4lxm Chain A Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4lxm Discovery of cyclic sulfoxide hydroxyethylamines as potent and selective beta-site APP-cleaving enzyme 1 (BACE1) inhibitors: structure based design and in vivo reduction of amyloid beta-peptides.
Resolution2.3 Å
Binding residue
(original residue number in PDB)		Q12 G13 L30 D32 G34 S35 P70 Y71 T72 F108 Y198 D228 G230
Binding residue
(residue number reindexed from 1)		Q15 G16 L33 D35 G37 S38 P73 Y74 T75 F111 Y190 D220 G222
Annotation score1
Binding affinityMOAD: ic50=0.088uM
PDBbind-CN: -logKd/Ki=7.06,IC50=0.088uM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
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:4lxm, PDBe:4lxm, PDBj:4lxm
PDBsum4lxm
PubMed23981898
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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