Structure of PDB 4lxk Chain A Binding Site BS01

Receptor Information
>4lxk Chain A (length=376) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPF
LHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRA
NIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVP
NLFSLQLCGSVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEIN
GQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPD
GFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPV
EDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSAC
HVHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID1YT
InChIInChI=1S/C27H36F4N2O4S/c1-26(2,3)19-7-5-6-16(9-19)12-33-21-15-38(35)14-18(25(21)34)8-17-10-20(28)24(32)22(11-17)37-23(13-36-4)27(29,30)31/h5-7,9-11,18,21,23,25,33-34H,8,12-15,32H2,1-4H3/t18-,21+,23-,25+,38-/m1/s1
InChIKeyFIUDDEQHPBHZBI-XPLIUGCLSA-N
SMILES
SoftwareSMILES
CACTVS 3.385COC[C@@H](Oc1cc(C[C@@H]2C[S@@](=O)C[C@H](NCc3cccc(c3)C(C)(C)C)[C@H]2O)cc(F)c1N)C(F)(F)F
OpenEye OEToolkits 1.7.6CC(C)(C)c1cccc(c1)CNC2CS(=O)CC(C2O)Cc3cc(c(c(c3)F)N)OC(COC)C(F)(F)F
CACTVS 3.385COC[CH](Oc1cc(C[CH]2C[S](=O)C[CH](NCc3cccc(c3)C(C)(C)C)[CH]2O)cc(F)c1N)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)O[C@H](COC)C(F)(F)F
ACDLabs 12.01O=S2CC(C(O)C(NCc1cccc(c1)C(C)(C)C)C2)Cc3cc(F)c(N)c(OC(C(F)(F)F)COC)c3
FormulaC27 H36 F4 N2 O4 S
Name(1R,3S,4S,5R)-3-(4-amino-3-fluoro-5-{[(2R)-1,1,1-trifluoro-3-methoxypropan-2-yl]oxy}benzyl)-5-[(3-tert-butylbenzyl)amino]tetrahydro-2H-thiopyran-4-ol 1-oxide
ChEMBLCHEMBL2425612
DrugBank
ZINCZINC000113540853
PDB chain4lxk 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

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
PDB4lxk 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.
Resolution2.05 Å
Binding residue
(original residue number in PDB)		Q12 G13 L30 D32 G34 S35 P70 Y71 T72 Q73 F108 I126 Y198 D228 G230 T231
Binding residue
(residue number reindexed from 1)		Q15 G16 L33 D35 G37 S38 P73 Y74 T75 Q76 F111 I129 Y189 D219 G221 T222
Annotation score1
Binding affinityMOAD: ic50=0.004uM
PDBbind-CN: -logKd/Ki=8.40,IC50=4nM
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 D219 T222
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

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:4lxk, PDBe:4lxk, PDBj:4lxk
PDBsum4lxk
PubMed23981898
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

[Back to BioLiP]