Structure of PDB 4b05 Chain A Binding Site BS01

Receptor Information
>4b05 Chain A (length=371) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPH
PFLHRYYQRQLSSTYRDLRKGVYVPYQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEING
QDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDG
FWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVE
DVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACH
DEFRTAAVEGPFVTLMEDCGY
Ligand information
Ligand ID32D
InChIInChI=1S/C24H16F3N5/c25-19-6-2-5-18-21(19)23(28)32-24(18,17-7-8-31-20(10-17)22(26)27)16-4-1-3-14(9-16)15-11-29-13-30-12-15/h1-13,22H,(H2,28,32)/t24-/m0/s1
InChIKeyMRXBCEQZNKUUIP-DEOSSOPVSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.9.2c1cc(cc(c1)[C@@]2(c3cccc(c3C(=N2)N)F)c4ccnc(c4)C(F)F)c5cncnc5
OpenEye OEToolkits 1.9.2c1cc(cc(c1)C2(c3cccc(c3C(=N2)N)F)c4ccnc(c4)C(F)F)c5cncnc5
CACTVS 3.385NC1=N[C](c2cccc(c2)c3cncnc3)(c4ccnc(c4)C(F)F)c5cccc(F)c15
ACDLabs 12.01FC(F)c1nccc(c1)C3(N=C(c2c(F)cccc23)N)c5cccc(c4cncnc4)c5
CACTVS 3.385NC1=N[C@@](c2cccc(c2)c3cncnc3)(c4ccnc(c4)C(F)F)c5cccc(F)c15
FormulaC24 H16 F3 N5
Name(1S)-1-[2-(difluoromethyl)pyridin-4-yl]-4-fluoro-1-(3-pyrimidin-5-ylphenyl)-1H-isoindol-3-amine
ChEMBLCHEMBL2177913
DrugBankDB12368
ZINCZINC000068205977
PDB chain4b05 Chain A Residue 1391 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
PDB4b05 Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		G13 L30 D32 S35 N37 Y71 W76 F108 I110 I118 D228 G230
Binding residue
(residue number reindexed from 1)		G18 L35 D37 S40 N42 Y76 W80 F112 I114 I122 D218 G220
Annotation score1
Binding affinityMOAD: Ki=26.1nM
PDBbind-CN: -logKd/Ki=7.58,Ki=26.1nM
BindingDB: IC50=0.600000nM,Ki=26nM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
Catalytic site (residue number reindexed from 1) D37 S40 N42 A44 Y76 D218 T221
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
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:4b05, PDBe:4b05, PDBj:4b05
PDBsum4b05
PubMed23048024
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

[Back to BioLiP]