Structure of PDB 4fse Chain A Binding Site BS01

Receptor Information
>4fse Chain A (length=387) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWY
YEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSI
KAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRI
TILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRA
RKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID0VA
InChIInChI=1S/C20H19Cl2N5O2S/c1-10-16(18(27-30-10)12-3-5-13(29-2)6-4-12)19(28)26-20(24)25-9-11-7-14(21)17(23)15(22)8-11/h3-8H,9,23H2,1-2H3,(H3,24,25,26,28)
InChIKeyDPJQBOWFYJTIJB-UHFFFAOYSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01Clc1cc(cc(Cl)c1N)CNC(=[N@H])NC(=O)c3c(snc3c2ccc(OC)cc2)C
OpenEye OEToolkits 1.7.6[H]/N=C(/NCc1cc(c(c(c1)Cl)N)Cl)\NC(=O)c2c(snc2c3ccc(cc3)OC)C
OpenEye OEToolkits 1.7.6Cc1c(c(ns1)c2ccc(cc2)OC)C(=O)NC(=N)NCc3cc(c(c(c3)Cl)N)Cl
CACTVS 3.370COc1ccc(cc1)c2nsc(C)c2C(=O)NC(=N)NCc3cc(Cl)c(N)c(Cl)c3
FormulaC20 H19 Cl2 N5 O2 S
NameN-[N-(4-amino-3,5-dichlorobenzyl)carbamimidoyl]-3-(4-methoxyphenyl)-5-methyl-1,2-thiazole-4-carboxamide
ChEMBLCHEMBL2178178
DrugBank
ZINCZINC000043151687
PDB chain4fse Chain A Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4fse Acyl guanidine inhibitors of beta-secretase (BACE-1): optimization of a micromolar hit to a nanomolar lead via iterative solid- and solution-phase library synthesis
Resolution2.65 Å
Binding residue
(original residue number in PDB)		D80 Y119 Q121 G122 F156 W163 Y246 I274 D276 G278 T279 R283 T377
Binding residue
(residue number reindexed from 1)		D34 Y73 Q75 G76 F110 W117 Y200 I228 D230 G232 T233 R237 T331
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=7.40,Ki=40nM
Enzymatic activity
Catalytic site (original residue number in PDB) D80 S83 N85 A87 Y119 D276 T279
Catalytic site (residue number reindexed from 1) D34 S37 N39 A41 Y73 D230 T233
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:4fse, PDBe:4fse, PDBj:4fse
PDBsum4fse
PubMed23030502
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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