Structure of PDB 4dpi Chain A Binding Site BS01

Receptor Information
>4dpi Chain A (length=373) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQ
DLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDGF
WLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVED
VATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHH
DEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID0N1
InChIInChI=1S/C34H41N3O4/c1-23(2)27-13-9-10-25(18-27)20-35-21-32(38)31-22-41-15-8-7-14-30(26-11-5-4-6-12-26)36-33(39)28-16-24(3)17-29(19-28)34(40)37-31/h4-13,16-19,23,30-32,35,38H,14-15,20-22H2,1-3H3,(H,36,39)(H,37,40)/b8-7+/t30-,31+,32-/m1/s1
InChIKeyBEGCWPHKTGGGNN-HOQOQLLYSA-N
SMILES
SoftwareSMILES
CACTVS 3.370CC(C)c1cccc(CNC[C@@H](O)[C@@H]2COC/C=C/C[C@@H](NC(=O)c3cc(C)cc(c3)C(=O)N2)c4ccccc4)c1
ACDLabs 12.01O=C2c4cc(C(=O)NC(COCC=CCC(c1ccccc1)N2)C(O)CNCc3cccc(c3)C(C)C)cc(c4)C
OpenEye OEToolkits 1.7.6Cc1cc2cc(c1)C(=O)NC(COCC=CCC(NC2=O)c3ccccc3)C(CNCc4cccc(c4)C(C)C)O
OpenEye OEToolkits 1.7.6Cc1cc2cc(c1)C(=O)N[C@@H](COC/C=C/C[C@@H](NC2=O)c3ccccc3)[C@@H](CNCc4cccc(c4)C(C)C)O
CACTVS 3.370CC(C)c1cccc(CNC[CH](O)[CH]2COCC=CC[CH](NC(=O)c3cc(C)cc(c3)C(=O)N2)c4ccccc4)c1
FormulaC34 H41 N3 O4
Name(4S,8E,11R)-4-[(1R)-1-hydroxy-2-{[3-(propan-2-yl)benzyl]amino}ethyl]-16-methyl-11-phenyl-6-oxa-3,12-diazabicyclo[12.3.1]octadeca-1(18),8,14,16-tetraene-2,13-dione
ChEMBLCHEMBL2047045
DrugBank
ZINCZINC000084653701
PDB chain4dpi 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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PDB4dpi Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: design, synthesis and X-ray crystal structures of enzyme inhibitor complexes.
Resolution1.9 Å
Binding residue
(original residue number in PDB)		G59 Q60 G61 L78 D80 G82 Y119 T120 Q121 D276 G278 T279 T280 A383
Binding residue
(residue number reindexed from 1)		G13 Q14 G15 L32 D34 G36 Y73 T74 Q75 D217 G219 T220 T221 A324
Annotation score1
Binding affinityMOAD: ic50=78nM
PDBbind-CN: -logKd/Ki=7.11,IC50=78nM
Enzymatic activity
Catalytic site (original residue number in PDB) D80 S83 N85 A87 Y119 D276 T279
Catalytic site (residue number reindexed from 1) D34 S37 N39 A41 Y73 D217 T220
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:4dpi, PDBe:4dpi, PDBj:4dpi
PDBsum4dpi
PubMed22698785
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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