Structure of PDB 4k9h Chain B Binding Site BS01

Receptor Information
>4k9h Chain B (length=369) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPF
LHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRA
NIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVP
NLFSLQLCGAVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEIN
GQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPD
GFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPV
DDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDEFR
TAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID1QU
InChIInChI=1S/C33H37F3N4O4/c34-33(35,36)25-11-6-10-23(16-25)19-37-20-29(41)27(17-22-8-2-1-3-9-22)38-31(43)24-18-28(39-15-7-14-30(39)42)32(44)40(21-24)26-12-4-5-13-26/h1-3,6,8-11,16,18,21,26-27,29,37,41H,4-5,7,12-15,17,19-20H2,(H,38,43)/t27-,29+/m0/s1
InChIKeyQKLJNYJRYSKKKP-LMSSTIIKSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6c1ccc(cc1)CC(C(CNCc2cccc(c2)C(F)(F)F)O)NC(=O)C3=CN(C(=O)C(=C3)N4CCCC4=O)C5CCCC5
OpenEye OEToolkits 1.7.6c1ccc(cc1)C[C@@H]([C@@H](CNCc2cccc(c2)C(F)(F)F)O)NC(=O)C3=CN(C(=O)C(=C3)N4CCCC4=O)C5CCCC5
CACTVS 3.370O[CH](CNCc1cccc(c1)C(F)(F)F)[CH](Cc2ccccc2)NC(=O)C3=CN(C4CCCC4)C(=O)C(=C3)N5CCCC5=O
ACDLabs 12.01FC(F)(F)c1cccc(c1)CNCC(O)C(NC(=O)C2=CN(C(=O)C(=C2)N3C(=O)CCC3)C4CCCC4)Cc5ccccc5
CACTVS 3.370O[C@H](CNCc1cccc(c1)C(F)(F)F)[C@H](Cc2ccccc2)NC(=O)C3=CN(C4CCCC4)C(=O)C(=C3)N5CCCC5=O
FormulaC33 H37 F3 N4 O4
Name1-cyclopentyl-N-[(2S,3R)-3-hydroxy-1-phenyl-4-{[3-(trifluoromethyl)benzyl]amino}butan-2-yl]-6-oxo-5-(2-oxopyrrolidin-1-yl)-1,6-dihydropyridine-3-carboxamide;
N-((1S,2R)-1-benzyl-2-hydroxy-3-((3-trifluoromethyl)benzyl)amino)propyl)-1-cyclopentyl-6-oxo-5-(2-oxo-1-pyrrolidinyl)-1,6-dihydro-3-pyridinecarboxamide
ChEMBLCHEMBL2407494
DrugBank
ZINCZINC000096273413
PDB chain4k9h Chain B Residue 401 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4k9h Hydroxyethylamine-based inhibitors of BACE1: P1-P3 macrocyclization can improve potency, selectivity, and cell activity.
Resolution2.29 Å
Binding residue
(original residue number in PDB)		Q12 D32 G34 S35 Y71 T72 Q73 F108 I110 I118 D228 G230 T232 N233
Binding residue
(residue number reindexed from 1)		Q15 D35 G37 S38 Y74 T75 Q76 F111 I113 I121 D219 G221 T223 N224
Annotation score1
Binding affinityMOAD: ic50=0.076uM
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

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4k9h, PDBe:4k9h, PDBj:4k9h
PDBsum4k9h
PubMed23769639
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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