Structure of PDB 4j17 Chain A Binding Site BS01

Receptor Information
>4j17 Chain A (length=379) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
RGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPH
PFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTV
RANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTH
VPNLFSLQLCGASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVASIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAV
SACHVHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID1HQ
InChIInChI=1S/C18H14F3N5O2/c19-13-3-2-11(25-15(27)14-4-1-10(8-22)9-24-14)7-12(13)18(16(20)21)5-6-28-17(23)26-18/h1-4,7,9,16H,5-6H2,(H2,23,26)(H,25,27)/t18-/m0/s1
InChIKeyZQBDXEARYNLKKR-SFHVURJKSA-N
SMILES
SoftwareSMILES
CACTVS 3.370NC1=N[C](CCO1)(C(F)F)c2cc(NC(=O)c3ccc(cn3)C#N)ccc2F
ACDLabs 12.01FC(F)C1(N=C(OCC1)N)c3cc(NC(=O)c2ncc(C#N)cc2)ccc3F
CACTVS 3.370NC1=N[C@](CCO1)(C(F)F)c2cc(NC(=O)c3ccc(cn3)C#N)ccc2F
OpenEye OEToolkits 1.7.6c1cc(c(cc1NC(=O)c2ccc(cn2)C#N)C3(CCOC(=N3)N)C(F)F)F
OpenEye OEToolkits 1.7.6c1cc(c(cc1NC(=O)c2ccc(cn2)C#N)[C@@]3(CCOC(=N3)N)C(F)F)F
FormulaC18 H14 F3 N5 O2
NameN-{3-[(4S)-2-amino-4-(difluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl]-4-fluorophenyl}-5-cyanopyridine-2-carboxamide
ChEMBLCHEMBL2347206
DrugBank
ZINCZINC000072315369
PDB chain4j17 Chain A Residue 504 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4j17 beta-Secretase (BACE1) Inhibitors with High In Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer s Disease
Resolution1.81 Å
Binding residue
(original residue number in PDB)		G72 Q73 G74 L91 D93 Y132 F169 I179 D289 G291 T293
Binding residue
(residue number reindexed from 1)		G16 Q17 G18 L35 D37 Y76 F113 I123 D222 G224 T226
Annotation score1
Binding affinityMOAD: ic50=0.054uM
PDBbind-CN: -logKd/Ki=7.27,IC50=54nM
BindingDB: IC50=46nM
Enzymatic activity
Catalytic site (original residue number in PDB) D93 S96 N98 A100 Y132 D289 T292
Catalytic site (residue number reindexed from 1) D37 S40 N42 A44 Y76 D222 T225
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:4j17, PDBe:4j17, PDBj:4j17
PDBsum4j17
PubMed23590342
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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