Structure of PDB 4i10 Chain A Binding Site BS03

Receptor Information
>4i10 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]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEI
NGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFP
DGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRP
VEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSA
CHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESRSHHHH
Ligand information
Ligand ID1BS
InChIInChI=1S/C26H24ClN5O/c1-26(2)14-17-13-18(27)8-9-19(17)23(32-26)30-22(12-16-6-4-3-5-7-16)24-29-21-10-11-28-15-20(21)25(33)31-24/h3-11,13,15,22H,12,14H2,1-2H3,(H,30,32)(H,29,31,33)/t22-/m0/s1
InChIKeyDQYKHJYAOKSEPD-QFIPXVFZSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC1(Cc2cc(ccc2C(=N1)NC(Cc3ccccc3)C4=NC(=O)c5cnccc5N4)Cl)C
ACDLabs 12.01Clc1cc2c(cc1)C(=NC(C)(C)C2)NC(C4=NC(=O)c3cnccc3N4)Cc5ccccc5
OpenEye OEToolkits 1.7.6CC1(Cc2cc(ccc2C(=N1)N[C@@H](Cc3ccccc3)C4=NC(=O)c5cnccc5N4)Cl)C
CACTVS 3.370CC1(C)Cc2cc(Cl)ccc2C(=N1)N[CH](Cc3ccccc3)C4=NC(=O)c5cnccc5N4
CACTVS 3.370CC1(C)Cc2cc(Cl)ccc2C(=N1)N[C@@H](Cc3ccccc3)C4=NC(=O)c5cnccc5N4
FormulaC26 H24 Cl N5 O
Name2-{(1S)-1-[(6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)amino]-2-phenylethyl}pyrido[4,3-d]pyrimidin-4(1H)-one
ChEMBLCHEMBL2346800
DrugBank
ZINCZINC000095603900
PDB chain4i10 Chain A Residue 504 [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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PDB4i10 Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.
Resolution2.07 Å
Binding residue
(original residue number in PDB)		Q73 G74 L91 Y132 Q134 G135 W176 G291 T292 T293 N294 R296
Binding residue
(residue number reindexed from 1)		Q14 G15 L32 Y73 Q75 G76 W117 G222 T223 T224 N225 R227
Annotation score1
Binding affinityMOAD: ic50=0.17uM
PDBbind-CN: -logKd/Ki=6.77,IC50=0.17uM
Enzymatic activity
Catalytic site (original residue number in PDB) D93 S96 N98 A100 Y132 D289 T292
Catalytic site (residue number reindexed from 1) D34 S37 N39 A41 Y73 D220 T223
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
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Biological Process
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Cellular Component
External links
PDB RCSB:4i10, PDBe:4i10, PDBj:4i10
PDBsum4i10
PubMed23465612
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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