Structure of PDB 4rro Chain A Binding Site BS01

Receptor Information
>4rro 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]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVR
VEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTE
KFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQY
LRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFA
VSACHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESRSHHHH
Ligand information
Ligand ID3UX
InChIInChI=1S/C21H21FN4O3/c1-20-8-4-10-28-17(20)21(18(27)26(2)19(23)25-21)14-11-12(6-7-15(14)29-20)13-5-3-9-24-16(13)22/h3,5-7,9,11,17H,4,8,10H2,1-2H3,(H2,23,25)/t17-,20-,21+/m1/s1
InChIKeyRYCBSDWTFORSET-UIFIKXQLSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC12CCCOC1C3(c4cc(ccc4O2)c5cccnc5F)C(=O)N(C(=N3)N)C
CACTVS 3.385CN1C(=N[C@@]2([C@@H]3OCCC[C@@]3(C)Oc4ccc(cc24)c5cccnc5F)C1=O)N
OpenEye OEToolkits 1.7.6C[C@@]12CCCO[C@H]1[C@@]3(c4cc(ccc4O2)c5cccnc5F)C(=O)N(C(=N3)N)C
CACTVS 3.385CN1C(=N[C]2([CH]3OCCC[C]3(C)Oc4ccc(cc24)c5cccnc5F)C1=O)N
ACDLabs 12.01Fc1ncccc1c5cc4c(OC2(CCCOC2C43N=C(N)N(C3=O)C)C)cc5
FormulaC21 H21 F N4 O3
Name(4S,4a'R,10a'S)-2-amino-8'-(2-fluoropyridin-3-yl)-1,4a'-dimethyl-3',4',4a',10a'-tetrahydro-2'H-spiro[imidazole-4,10'-pyrano[3,2-b]chromen]-5(1H)-one
ChEMBLCHEMBL3357659
DrugBank
ZINCZINC000144267411
PDB chain4rro Chain A Residue 502 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4rro 8-Tetrahydropyran-2-yl Chromans: Highly Selective Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitors.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		G72 Q73 G74 L91 D93 Y132 F169 I171 W176 I179 D289 G291
Binding residue
(residue number reindexed from 1)		G13 Q14 G15 L32 D34 Y73 F110 I112 W117 I120 D223 G225
Annotation score1
Binding affinityMOAD: ic50=26nM
PDBbind-CN: -logKd/Ki=7.59,IC50=26nM
BindingDB: IC50=26nM
Enzymatic activity
Catalytic site (original residue number in PDB) D93 S96 N98 A100 Y132 D289 T292
Catalytic site (residue number reindexed from 1) D34 S37 N39 A41 Y73 D223 T226
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:4rro, PDBe:4rro, PDBj:4rro
PDBsum4rro
PubMed25411915
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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