Structure of PDB 2qzk Chain A Binding Site BS01

Receptor Information
>2qzk Chain A (length=376) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPF
LHRYYQRQLSSTYRDLRKGVYVPYTQGAWAGELGTDLVSIPHGPNVTVRA
NIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVP
NLFSLQLCGAVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEIN
GQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPD
GFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPV
EDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSAC
HVHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand IDI21
InChIInChI=1S/C34H27N3O3/c1-34(36)20-24-9-7-8-23(16-24)14-15-31(26-10-3-2-4-11-26)37-32(38)29-18-25(22-40-33(34)39)17-28(19-29)30-13-6-5-12-27(30)21-35/h2-19H,20,22,36H2,1H3/t34-/m1/s1
InChIKeyGWSQLGYWQZHSHS-UUWRZZSWSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.5.0CC1(Cc2cccc(c2)C=CC(=NC(=O)c3cc(cc(c3)c4ccccc4C#N)COC1=O)c5ccccc5)N
CACTVS 3.341C[C@@]1(N)Cc2cccc(\C=C/C(=NC(=O)c3cc(COC1=O)cc(c3)c4ccccc4C#N)c5ccccc5)c2
OpenEye OEToolkits 1.5.0C[C@]1(Cc2cccc(c2)C=CC(=NC(=O)c3cc(cc(c3)c4ccccc4C#N)COC1=O)c5ccccc5)N
ACDLabs 10.04N#Cc5ccccc5c3cc4C(=O)N=C(c1ccccc1)C=Cc2cccc(c2)CC(N)(C(=O)OCc(c3)c4)C
CACTVS 3.341C[C]1(N)Cc2cccc(C=CC(=NC(=O)c3cc(COC1=O)cc(c3)c4ccccc4C#N)c5ccccc5)c2
FormulaC34 H27 N3 O3
Name2-[(5R)-5-amino-5-methyl-4,16-dioxo-14-phenyl-3-oxa-15-azatricyclo[15.3.1.1~7,11~]docosa-1(21),7(22),8,10,12,14,17,19-octaen-19-yl]benzonitrile
ChEMBL
DrugBank
ZINCZINC000263620486
PDB chain2qzk Chain A Residue 400 [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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PDB2qzk Strategies toward improving the brain penetration of macrocyclic tertiary carbinamine BACE-1 inhibitors.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		G11 Q12 G13 L30 D32 G34 Y71 T72 Q73 W115 D228 S229 G230 T231 T232 N233
Binding residue
(residue number reindexed from 1)		G14 Q15 G16 L33 D35 G37 Y74 T75 Q76 W118 D219 S220 G221 T222 T223 N224
Annotation score1
Binding affinityMOAD: ic50=27nM
PDBbind-CN: -logKd/Ki=7.57,IC50=27nM
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:2qzk, PDBe:2qzk, PDBj:2qzk
PDBsum2qzk
PubMed17827011
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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