Structure of PDB 4wtu Chain A Binding Site BS01

Receptor Information
>4wtu 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]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGAASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEI
NGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFP
DGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRP
VEDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDE
FRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID3UT
InChIInChI=1S/C24H18F2N4O3/c25-21-15(4-1-7-28-21)13-5-6-19-16(9-13)24(12-32-23(27)30-24)17-10-18(14-3-2-8-31-11-14)29-22(26)20(17)33-19/h1,3-7,9-10H,2,8,11-12H2,(H2,27,30)/t24-/m0/s1
InChIKeyJAZOCUNZCUBRJX-DEOSSOPVSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.9.2c1cc(c(nc1)F)c2ccc3c(c2)[C@@]4(COC(=N4)N)c5cc(nc(c5O3)F)C6=CCCOC6
CACTVS 3.385NC1=N[C]2(CO1)c3cc(ccc3Oc4c(F)nc(cc24)C5=CCCOC5)c6cccnc6F
CACTVS 3.385NC1=N[C@@]2(CO1)c3cc(ccc3Oc4c(F)nc(cc24)C5=CCCOC5)c6cccnc6F
OpenEye OEToolkits 1.9.2c1cc(c(nc1)F)c2ccc3c(c2)C4(COC(=N4)N)c5cc(nc(c5O3)F)C6=CCCOC6
ACDLabs 12.01Fc1ncccc1c6cc5c(Oc3c(F)nc(C2=CCCOC2)cc3C54N=C(OC4)N)cc6
FormulaC24 H18 F2 N4 O3
Name(5S)-3-(5,6-dihydro-2H-pyran-3-yl)-1-fluoro-7-(2-fluoropyridin-3-yl)spiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazol]-2'-amine
ChEMBLCHEMBL4564735
DrugBank
ZINCZINC000072317156
PDB chain4wtu Chain A Residue 407 [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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PDB4wtu An Orally Available BACE1 Inhibitor That Affords Robust CNS A beta Reduction without Cardiovascular Liabilities.
Resolution1.85 Å
Binding residue
(original residue number in PDB)		G11 Q12 G13 L30 D32 S35 Y71 W76 F108 I118 R128 D228 G230
Binding residue
(residue number reindexed from 1)		G13 Q14 G15 L32 D34 S37 Y73 W78 F110 I120 R130 D220 G222
Annotation score1
Binding affinityMOAD: ic50=0.3nM
PDBbind-CN: -logKd/Ki=9.52,IC50=0.3nM
BindingDB: IC50=3.0nM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
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:4wtu, PDBe:4wtu, PDBj:4wtu
PDBsum4wtu
PubMed25699151
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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