Structure of PDB 4j1e Chain A Binding Site BS01

Receptor Information
>4j1e 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 ID1HM
InChIInChI=1S/C19H14F5N5O2/c20-9-18(6-15(19(22,23)24)31-17(26)29-18)12-5-11(2-3-13(12)21)28-16(30)14-4-1-10(7-25)8-27-14/h1-5,8,15H,6,9H2,(H2,26,29)(H,28,30)/t15-,18+/m0/s1
InChIKeyQCMXWFUAVCHHIA-MAUKXSAKSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01FC(F)(F)C3OC(=NC(c2cc(NC(=O)c1ncc(C#N)cc1)ccc2F)(CF)C3)N
OpenEye OEToolkits 1.7.6c1cc(c(cc1NC(=O)c2ccc(cn2)C#N)C3(CC(OC(=N3)N)C(F)(F)F)CF)F
OpenEye OEToolkits 1.7.6c1cc(c(cc1NC(=O)c2ccc(cn2)C#N)[C@@]3(C[C@H](OC(=N3)N)C(F)(F)F)CF)F
CACTVS 3.370NC1=N[C](CF)(C[CH](O1)C(F)(F)F)c2cc(NC(=O)c3ccc(cn3)C#N)ccc2F
CACTVS 3.370NC1=N[C@@](CF)(C[C@H](O1)C(F)(F)F)c2cc(NC(=O)c3ccc(cn3)C#N)ccc2F
FormulaC19 H14 F5 N5 O2
NameN-{3-[(4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl]-4-fluorophenyl}-5-cyanopyridine-2-carboxamide
ChEMBLCHEMBL2347187
DrugBank
ZINCZINC000095602098
PDB chain4j1e 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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PDB4j1e beta-Secretase (BACE1) Inhibitors with High In Vivo Efficacy Suitable for Clinical Evaluation in Alzheimer s Disease
Resolution1.78 Å
Binding residue
(original residue number in PDB)		G72 Q73 G74 L91 D93 S96 Y132 F169 I179 D289 G291 T293
Binding residue
(residue number reindexed from 1)		G16 Q17 G18 L35 D37 S40 Y76 F113 I123 D222 G224 T226
Annotation score1
Binding affinityMOAD: ic50=0.019uM
PDBbind-CN: -logKd/Ki=7.72,IC50=19nM
BindingDB: IC50=17.9nM
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:4j1e, PDBe:4j1e, PDBj:4j1e
PDBsum4j1e
PubMed23590342
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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