Structure of PDB 4hzt Chain A Binding Site BS04

Receptor Information
>4hzt Chain A (length=393) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAV
SACHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESRSHHHHH
Ligand information
Ligand ID0ZA
InChIInChI=1S/C21H21ClN4O2/c1-21(2)12-14-11-15(22)8-9-16(14)18(25-21)23-17(19-24-20(27)28-26-19)10-13-6-4-3-5-7-13/h3-9,11,17H,10,12H2,1-2H3,(H,23,25)(H,24,26,27)/t17-/m0/s1
InChIKeyXREOSEVJCQGCHE-KRWDZBQOSA-N
SMILES
SoftwareSMILES
CACTVS 3.370CC1(C)Cc2cc(Cl)ccc2C(=N1)N[CH](Cc3ccccc3)C4=NC(=O)ON4
OpenEye OEToolkits 1.7.6CC1(Cc2cc(ccc2C(=N1)NC(Cc3ccccc3)C4=NC(=O)ON4)Cl)C
CACTVS 3.370CC1(C)Cc2cc(Cl)ccc2C(=N1)N[C@@H](Cc3ccccc3)C4=NC(=O)ON4
ACDLabs 12.01Clc4cc1c(C(=NC(C)(C)C1)NC(C2=NC(=O)ON2)Cc3ccccc3)cc4
OpenEye OEToolkits 1.7.6CC1(Cc2cc(ccc2C(=N1)N[C@@H](Cc3ccccc3)C4=NC(=O)ON4)Cl)C
FormulaC21 H21 Cl N4 O2
Name3-{(1S)-1-[(6-chloro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)amino]-2-phenylethyl}-1,2,4-oxadiazol-5(2H)-one
ChEMBLCHEMBL2346796
DrugBank
ZINCZINC000095605836
PDB chain4hzt 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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PDB4hzt 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 Q134 G135 F169 W176 G291 T292 T293 N294
Binding residue
(residue number reindexed from 1)		Q16 G17 L34 D36 Y75 Q77 G78 F112 W119 G224 T225 T226 N227
Annotation score1
Binding affinityMOAD: ic50=0.75uM
PDBbind-CN: -logKd/Ki=6.12,IC50=0.75uM
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 D222 T225
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:4hzt, PDBe:4hzt, PDBj:4hzt
PDBsum4hzt
PubMed23465612
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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