Structure of PDB 3lpk Chain A Binding Site BS01

Receptor Information
>3lpk Chain A (length=390) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRRE
WYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVK
SIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSF
RITILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFD
RARKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNI
Ligand information
Ligand IDZ76
InChIInChI=1S/C35H42F2N4O6S/c1-22-6-4-8-30(14-22)48(45,46)40-11-9-38-32(20-40)33(42)31(17-24-15-27(36)19-28(37)16-24)39-34(43)25-12-23(2)13-26(18-25)35(44)41-10-5-7-29(41)21-47-3/h4,6,8,12-16,18-19,29,31-33,38,42H,5,7,9-11,17,20-21H2,1-3H3,(H,39,43)/t29-,31+,32-,33+/m1/s1
InChIKeyCQQMWBPWYUPVOC-PPESYSCFSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.0Cc1cccc(c1)S(=O)(=O)[N@]2CCN[C@H](C2)[C@H]([C@H](Cc3cc(cc(c3)F)F)NC(=O)c4cc(cc(c4)C(=O)N5CCC[C@@H]5COC)C)O
CACTVS 3.352COC[CH]1CCCN1C(=O)c2cc(C)cc(c2)C(=O)N[CH](Cc3cc(F)cc(F)c3)[CH](O)[CH]4CN(CCN4)[S](=O)(=O)c5cccc(C)c5
CACTVS 3.352COC[C@H]1CCCN1C(=O)c2cc(C)cc(c2)C(=O)N[C@@H](Cc3cc(F)cc(F)c3)[C@H](O)[C@H]4CN(CCN4)[S](=O)(=O)c5cccc(C)c5
OpenEye OEToolkits 1.7.0Cc1cccc(c1)S(=O)(=O)N2CCNC(C2)C(C(Cc3cc(cc(c3)F)F)NC(=O)c4cc(cc(c4)C(=O)N5CCCC5COC)C)O
FormulaC35 H42 F2 N4 O6 S
NameN-[(1S,2S)-1-(3,5-difluorobenzyl)-2-hydroxy-2-{(2R)-4-[(3-methylphenyl)sulfonyl]piperazin-2-yl}ethyl]-3-{[(2R)-2-(methoxymethyl)pyrrolidin-1-yl]carbonyl}-5-methylbenzamide
ChEMBLCHEMBL1097342
DrugBank
ZINCZINC000049802648
PDB chain3lpk Chain A Residue 456 [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]
PDB3lpk Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization.
Resolution1.93 Å
Binding residue
(original residue number in PDB)		G72 D93 G95 Y132 T133 Q134 G135 F169 I171 R189 Y259 D289 G291 T293
Binding residue
(residue number reindexed from 1)		G15 D36 G38 Y75 T76 Q77 G78 F112 I114 R132 Y202 D232 G234 T236
Annotation score1
Binding affinityMOAD: Ki=0.8nM
PDBbind-CN: -logKd/Ki=9.10,Ki=0.8nM
BindingDB: IC50=7nM,Ki=0.800000nM
Enzymatic activity
Catalytic site (original residue number in PDB) D93 S96 N98 A100 Y132 D289 T292
Catalytic site (residue number reindexed from 1) D36 S39 N41 A43 Y75 D232 T235
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:3lpk, PDBe:3lpk, PDBj:3lpk
PDBsum3lpk
PubMed20347593
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

[Back to BioLiP]