Structure of PDB 4b00 Chain A Binding Site BS01

Receptor Information
>4b00 Chain A (length=375) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGAGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEIN
GQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPD
GFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPV
EDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSAC
HVHDEFRTAAVEGPFVTLDMEDCGY
Ligand information
Ligand IDI6X
InChIInChI=1S/C30H25FN4O/c1-4-8-20-14-22(17-33-16-20)21-9-6-10-23(15-21)30(24-13-19(3)29(36)35(5-2)18-24)25-11-7-12-26(31)27(25)28(32)34-30/h6-7,9-18H,5H2,1-3H3,(H2,32,34)/t30-/m0/s1
InChIKeyTUGLMYZSOPKJOA-PMERELPUSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CCN1C=C(C=C(C)C1=O)[C@@]2(N=C(N)c3c(F)cccc23)c4cccc(c4)c5cncc(c5)C#CC
OpenEye OEToolkits 1.9.2CCN1C=C(C=C(C1=O)C)C2(c3cccc(c3C(=N2)N)F)c4cccc(c4)c5cc(cnc5)C#CC
CACTVS 3.385CCN1C=C(C=C(C)C1=O)[C]2(N=C(N)c3c(F)cccc23)c4cccc(c4)c5cncc(c5)C#CC
OpenEye OEToolkits 1.9.2CCN1C=C(C=C(C1=O)C)[C@]2(c3cccc(c3C(=N2)N)F)c4cccc(c4)c5cc(cnc5)C#CC
ACDLabs 12.01O=C1C(=CC(=CN1CC)C3(N=C(N)c2c3cccc2F)c5cccc(c4cc(C#CC)cnc4)c5)C
FormulaC30 H25 F N4 O
Name5-{(1R)-3-amino-4-fluoro-1-[3-(5-prop-1-yn-1-ylpyridin-3-yl)phenyl]-1H-isoindol-1-yl}-1-ethyl-3-methylpyridin-2(1H)-one
ChEMBLCHEMBL2152903
DrugBank
ZINC
PDB chain4b00 Chain A Residue 1507 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4b00 Design and synthesis of beta-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors with in vivo brain reduction of beta-amyloid peptides.
Resolution1.83 Å
Binding residue
(original residue number in PDB)		S10 Q12 G13 D32 S35 Y71 W76 F108 I110 I118 D228 S229 G230 T231
Binding residue
(residue number reindexed from 1)		S14 Q16 G17 D36 S39 Y75 W80 F112 I114 I122 D219 S220 G221 T222
Annotation score1
Binding affinityMOAD: ic50=2.44nM
PDBbind-CN: -logKd/Ki=8.61,IC50=2.44nM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
Catalytic site (residue number reindexed from 1) D36 S39 N41 A43 Y75 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:4b00, PDBe:4b00, PDBj:4b00
PDBsum4b00
PubMed22924815
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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