Structure of PDB 3lpi Chain A Binding Site BS01

Receptor Information
>3lpi 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 IDZ74
InChIInChI=1S/C34H42F2N4O5S/c1-4-12-39(13-5-2)34(43)26-16-23(3)15-25(20-26)33(42)38-30(19-24-17-27(35)21-28(36)18-24)32(41)31-22-40(14-11-37-31)46(44,45)29-9-7-6-8-10-29/h6-10,15-18,20-21,30-32,37,41H,4-5,11-14,19,22H2,1-3H3,(H,38,42)/t30-,31+,32-/m0/s1
InChIKeyKDRUCCZCGHVXGH-QAXCHELISA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.0CCCN(CCC)C(=O)c1cc(cc(c1)C(=O)NC(Cc2cc(cc(c2)F)F)C(C3CN(CCN3)S(=O)(=O)c4ccccc4)O)C
OpenEye OEToolkits 1.7.0CCCN(CCC)C(=O)c1cc(cc(c1)C(=O)N[C@@H](Cc2cc(cc(c2)F)F)[C@@H]([C@H]3C[N@](CCN3)S(=O)(=O)c4ccccc4)O)C
ACDLabs 12.01O=S(=O)(c1ccccc1)N2CC(NCC2)C(O)C(NC(=O)c3cc(cc(C(=O)N(CCC)CCC)c3)C)Cc4cc(F)cc(F)c4
CACTVS 3.370CCCN(CCC)C(=O)c1cc(C)cc(c1)C(=O)N[CH](Cc2cc(F)cc(F)c2)[CH](O)[CH]3CN(CCN3)[S](=O)(=O)c4ccccc4
CACTVS 3.370CCCN(CCC)C(=O)c1cc(C)cc(c1)C(=O)N[C@@H](Cc2cc(F)cc(F)c2)[C@H](O)[C@H]3CN(CCN3)[S](=O)(=O)c4ccccc4
FormulaC34 H42 F2 N4 O5 S
NameN'-{(1S,2S)-1-(3,5-difluorobenzyl)-2-hydroxy-2-[(2R)-4-(phenylsulfonyl)piperazin-2-yl]ethyl}-5-methyl-N,N-dipropylbenzene-1,3-dicarboxamide
ChEMBLCHEMBL1097319
DrugBank
ZINCZINC000049784328
PDB chain3lpi 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

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PDB3lpi Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization.
Resolution2.05 Å
Binding residue
(original residue number in PDB)		G72 D93 G95 Y132 T133 Q134 F169 R189 Y259 D289 G291 T293
Binding residue
(residue number reindexed from 1)		G15 D36 G38 Y75 T76 Q77 F112 R132 Y202 D232 G234 T236
Annotation score1
Binding affinityMOAD: Ki=3nM
PDBbind-CN: -logKd/Ki=8.52,Ki=3nM
BindingDB: IC50=120nM,Ki=3nM
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

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:3lpi, PDBe:3lpi, PDBj:3lpi
PDBsum3lpi
PubMed20347593
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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