Structure of PDB 4n00 Chain A Binding Site BS01

Receptor Information
>4n00 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 ID2EX
InChIInChI=1S/C20H19FN4O3/c1-25-18(26)20(24-19(25)22)13-9-11(12-3-2-7-23-17(12)21)4-5-15(13)28-16-6-8-27-10-14(16)20/h2-5,7,9,14,16H,6,8,10H2,1H3,(H2,22,24)/t14-,16-,20-/m0/s1
InChIKeyDWEUDIDNAOSEBW-UVFQYZLESA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CN1C(=O)C2(c3cc(ccc3OC4C2COCC4)c5cccnc5F)N=C1N
OpenEye OEToolkits 1.7.6CN1C(=O)[C@@]2(c3cc(ccc3O[C@@H]4[C@@H]2COCC4)c5cccnc5F)N=C1N
CACTVS 3.385CN1C(=N[C@@]2([C@H]3COCC[C@@H]3Oc4ccc(cc24)c5cccnc5F)C1=O)N
ACDLabs 12.01Fc1ncccc1c5cc3c(OC4C(C32N=C(N)N(C2=O)C)COCC4)cc5
CACTVS 3.385CN1C(=N[C]2([CH]3COCC[CH]3Oc4ccc(cc24)c5cccnc5F)C1=O)N
FormulaC20 H19 F N4 O3
Name(4R,4a'S,10a'S)-2-amino-8'-(2-fluoropyridin-3-yl)-1-methyl-3',4',4a',10a'-tetrahydro-1'H-spiro[imidazole-4,10'-pyrano[4,3-b]chromen]-5(1H)-one
ChEMBLCHEMBL3127106
DrugBank
ZINCZINC000098208158
PDB chain4n00 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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PDB4n00 Discovery of 7-tetrahydropyran-2-yl chromans: beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors that reduce amyloid beta-protein (A beta ) in the central nervous system.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		G72 Q73 G74 L91 D93 Y132 W137 F169 W176 D289 G291
Binding residue
(residue number reindexed from 1)		G13 Q14 G15 L32 D34 Y73 W78 F110 W117 D223 G225
Annotation score1
Binding affinityMOAD: ic50=9.5nM
PDBbind-CN: -logKd/Ki=8.02,IC50=9.5nM
BindingDB: IC50=9.9nM
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:4n00, PDBe:4n00, PDBj:4n00
PDBsum4n00
PubMed24397738
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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