Structure of PDB 4jpc Chain A Binding Site BS01

Receptor Information
>4jpc Chain A (length=402) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRRE
WYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVK
SIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSF
RITILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFD
RARKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESRSHH
HH
Ligand information
Ligand ID1M6
InChIInChI=1S/C21H20N4O2/c1-20(2)12-21(18(26)25(3)19(23)24-21)16-10-15(7-8-17(16)27-20)14-6-4-5-13(9-14)11-22/h4-10H,12H2,1-3H3,(H2,23,24)/t21-/m1/s1
InChIKeyLASIJFPKQNWUQE-OAQYLSRUSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC1(C[C@@]2(c3cc(ccc3O1)c4cccc(c4)C#N)C(=O)N(C(=N2)N)C)C
ACDLabs 12.01N#Cc1cccc(c1)c4ccc3OC(CC2(N=C(N(C2=O)C)N)c3c4)(C)C
CACTVS 3.370CN1C(=N[C]2(CC(C)(C)Oc3ccc(cc23)c4cccc(c4)C#N)C1=O)N
OpenEye OEToolkits 1.7.6CC1(CC2(c3cc(ccc3O1)c4cccc(c4)C#N)C(=O)N(C(=N2)N)C)C
CACTVS 3.370CN1C(=N[C@@]2(CC(C)(C)Oc3ccc(cc23)c4cccc(c4)C#N)C1=O)N
FormulaC21 H20 N4 O2
Name3-[(4R)-2'-amino-1',2,2-trimethyl-5'-oxo-1',2,3,5'-tetrahydrospiro[chromene-4,4'-imidazol]-6-yl]benzonitrile
ChEMBL
DrugBank
ZINCZINC000095605902
PDB chain4jpc 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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PDB4jpc Spirocyclic beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors: from hit to lowering of cerebrospinal fluid (CSF) amyloid beta in a higher species.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		Q60 G61 D80 S83 Y119 F156 I158 I166 D276 G278 T279
Binding residue
(residue number reindexed from 1)		Q16 G17 D36 S39 Y75 F112 I114 I122 D232 G234 T235
Annotation score1
Binding affinityMOAD: ic50=94nM
PDBbind-CN: -logKd/Ki=7.03,IC50=94nM
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 D232 T235
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:4jpc, PDBe:4jpc, PDBj:4jpc
PDBsum4jpc
PubMed23537249
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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