Structure of PDB 5tol Chain A Binding Site BS01

Receptor Information
>5tol Chain A (length=374) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGSVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEI
NGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFP
DGFWLGEQLVCWQATTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPV
EDVATSDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHV
HDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID7H3
InChIInChI=1S/C18H16BrFN4O2S/c19-11-1-4-15(22-8-11)16(25)23-12-2-3-14(20)13(7-12)18-10(5-6-26-18)9-27-17(21)24-18/h1-4,7-8,10H,5-6,9H2,(H2,21,24)(H,23,25)/t10-,18+/m0/s1
InChIKeyDACRJCISVSMZQT-XTZNXHDOSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.6c1cc(c(cc1NC(=O)c2ccc(cn2)Br)C34C(CCO3)CSC(=N4)N)F
CACTVS 3.385NC1=N[C@]2(OCC[C@H]2CS1)c3cc(NC(=O)c4ccc(Br)cn4)ccc3F
ACDLabs 12.01c4(Br)ccc(C(Nc3ccc(c(C12C(CSC(N)=N1)CCO2)c3)F)=O)nc4
OpenEye OEToolkits 2.0.6c1cc(c(cc1NC(=O)c2ccc(cn2)Br)[C@@]34[C@@H](CCO3)CSC(=N4)N)F
CACTVS 3.385NC1=N[C]2(OCC[CH]2CS1)c3cc(NC(=O)c4ccc(Br)cn4)ccc3F
FormulaC18 H16 Br F N4 O2 S
NameN-{3-[(4aR,7aR)-2-amino-4,4a,5,6-tetrahydro-7aH-furo[2,3-d][1,3]thiazin-7a-yl]-4-fluorophenyl}-5-bromopyridine-2-carboxamide
ChEMBLCHEMBL3919597
DrugBank
ZINCZINC000145711034
PDB chain5tol Chain A Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
PDB5tol Discovery of furo[2,3-d][1,3]thiazinamines as beta amyloid cleaving enzyme-1 (BACE1) inhibitors.
Resolution2.51 Å
Binding residue
(original residue number in PDB)		G59 G61 L78 D80 Y119 F156 D276 S277 G278 T280
Binding residue
(residue number reindexed from 1)		G15 G17 L34 D36 Y75 F112 D220 S221 G222 T224
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=7.48,IC50=33nM
BindingDB: IC50=33nM
Enzymatic activity
Catalytic site (original residue number in PDB) D80 S83 N85 A87 Y119 D276 T279
Catalytic site (residue number reindexed from 1) D36 S39 N41 A43 Y75 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

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:5tol, PDBe:5tol, PDBj:5tol
PDBsum5tol
PubMed27816517
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

[Back to BioLiP]