Structure of PDB 4i0z Chain A Binding Site BS01

Receptor Information
>4i0z 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 ID1BB
InChIInChI=1S/C24H22ClN5O/c1-24(2)12-16-11-18(25)8-9-19(16)21(30-24)28-20(10-15-6-4-3-5-7-15)22-27-14-17(13-26)23(31)29-22/h3-9,11,14,20H,10,12H2,1-2H3,(H,28,30)(H,27,29,31)/t20-/m0/s1
InChIKeySSQLUPVACAMCTQ-FQEVSTJZSA-N
SMILES
SoftwareSMILES
CACTVS 3.370CC1(C)Cc2cc(Cl)ccc2C(=N1)N[CH](Cc3ccccc3)C4=NC(=O)C(=CN4)C#N
OpenEye OEToolkits 1.7.6CC1(Cc2cc(ccc2C(=N1)N[C@@H](Cc3ccccc3)C4=NC(=O)C(=CN4)C#N)Cl)C
ACDLabs 12.01Clc4cc1c(C(=NC(C)(C)C1)NC(C2=NC(=O)C(C#N)=CN2)Cc3ccccc3)cc4
CACTVS 3.370CC1(C)Cc2cc(Cl)ccc2C(=N1)N[C@@H](Cc3ccccc3)C4=NC(=O)C(=CN4)C#N
OpenEye OEToolkits 1.7.6CC1(Cc2cc(ccc2C(=N1)NC(Cc3ccccc3)C4=NC(=O)C(=CN4)C#N)Cl)C
FormulaC24 H22 Cl N5 O
Name2-{(1S)-1-[(6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)amino]-2-phenylethyl}-4-oxo-1,4-dihydropyrimidine-5-carbonitrile
ChEMBLCHEMBL2346802
DrugBank
ZINCZINC000095602622
PDB chain4i0z Chain A Residue 501 [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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PDB4i0z Structure-based design of novel dihydroisoquinoline BACE-1 inhibitors that do not engage the catalytic aspartates.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		Q73 G74 L91 D93 Y132 G135 K168 F169 G291 T292 T293 N294 R296
Binding residue
(residue number reindexed from 1)		Q14 G15 L32 D34 Y73 G76 K109 F110 G222 T223 T224 N225 R227
Annotation score1
Binding affinityMOAD: ic50=0.47uM
PDBbind-CN: -logKd/Ki=6.33,IC50=0.47uM
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

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4i0z, PDBe:4i0z, PDBj:4i0z
PDBsum4i0z
PubMed23465612
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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