Structure of PDB 6pz4 Chain A Binding Site BS01

Receptor Information
>6pz4 Chain A (length=380) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGAVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAV
SACHVHDEFRTAAVEGPFVTLDMEDCGYNI
Ligand information
Ligand IDP6J
InChIInChI=1S/C22H21F2N5O3S/c1-4-5-32-17-10-26-15(9-27-17)19(30)28-12-6-13(18(24)14(23)7-12)21(2)16-8-22(16,11-31-3)33-20(25)29-21/h1,6-7,9-10,16H,5,8,11H2,2-3H3,(H2,25,29)(H,28,30)/t16-,21+,22+/m0/s1
InChIKeyIPUJINDWAGRAHN-KNXBSLHKSA-N
SMILES
SoftwareSMILES
CACTVS 3.385COC[C]12C[CH]1[C](C)(N=C(N)S2)c3cc(NC(=O)c4cnc(OCC#C)cn4)cc(F)c3F
OpenEye OEToolkits 2.0.7CC1(C2CC2(SC(=N1)N)COC)c3cc(cc(c3F)F)NC(=O)c4cnc(cn4)OCC#C
ACDLabs 12.01COCC12C(C1)C(N=C(S2)N)(C)c3c(F)c(F)cc(c3)NC(=O)c4cnc(cn4)OCC#C
OpenEye OEToolkits 2.0.7C[C@]1([C@@H]2C[C@@]2(SC(=N1)N)COC)c3cc(cc(c3F)F)NC(=O)c4cnc(cn4)OCC#C
CACTVS 3.385COC[C@]12C[C@H]1[C@](C)(N=C(N)S2)c3cc(NC(=O)c4cnc(OCC#C)cn4)cc(F)c3F
FormulaC22 H21 F2 N5 O3 S
NameN-{3-[(1S,5S,6S)-3-amino-1-(methoxymethyl)-5-methyl-2-thia-4-azabicyclo[4.1.0]hept-3-en-5-yl]-4,5-difluorophenyl}-5-[(prop-2-yn-1-yl)oxy]pyrazine-2-carboxamide
ChEMBLCHEMBL4560579
DrugBank
ZINC
PDB chain6pz4 Chain A Residue 506 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB6pz4 Discovery of AM-6494: A Potent and Orally Efficacious beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor with in Vivo Selectivity over BACE2.
Resolution1.85 Å
Binding residue
(original residue number in PDB)		G72 G74 Y75 D93 Y132 F169 D289 G291 T292 T293 A396
Binding residue
(residue number reindexed from 1)		G13 G15 Y16 D34 Y73 F110 D222 G224 T225 T226 A329
Annotation score1
Binding affinityMOAD: ic50=0.4nM
PDBbind-CN: -logKd/Ki=9.40,IC50=0.0004uM
BindingDB: IC50=1.2nM
Enzymatic activity
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:6pz4, PDBe:6pz4, PDBj:6pz4
PDBsum6pz4
PubMed31589043
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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