Structure of PDB 4pzw Chain A Binding Site BS01

Receptor Information
>4pzw Chain A (length=397) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
RGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPH
PFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTV
RANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTH
VPNLFSLQLCGASEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEV
IIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAA
SSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITIL
PQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKR
IGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESRSHHHH
Ligand information
Ligand ID2X4
InChIInChI=1S/C19H18ClN3O3/c20-13-5-12(7-22-8-13)11-1-2-16-15(6-11)19(10-25-18(21)23-19)14-3-4-24-9-17(14)26-16/h1-2,5-8,14,17H,3-4,9-10H2,(H2,21,23)/t14-,17-,19-/m1/s1
InChIKeyBGRWOLNAPSRJIS-LSBZLQRGSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01Clc1cc(cnc1)c5cc3c(OC4COCCC4C32N=C(OC2)N)cc5
CACTVS 3.385NC1=N[C]2(CO1)[CH]3CCOC[CH]3Oc4ccc(cc24)c5cncc(Cl)c5
CACTVS 3.385NC1=N[C@]2(CO1)[C@@H]3CCOC[C@H]3Oc4ccc(cc24)c5cncc(Cl)c5
OpenEye OEToolkits 1.7.6c1cc2c(cc1c3cc(cnc3)Cl)C4(COC(=N4)N)C5CCOCC5O2
OpenEye OEToolkits 1.7.6c1cc2c(cc1c3cc(cnc3)Cl)[C@@]4(COC(=N4)N)[C@@H]5CCOC[C@H]5O2
FormulaC19 H18 Cl N3 O3
Name(4R,4a'S,10a'S)-7'-(5-chloropyridin-3-yl)-3',4',4a',10a'-tetrahydro-1'H-spiro[1,3-oxazole-4,5'-pyrano[3,4-b]chromen]-2-amine
ChEMBLCHEMBL3265330
DrugBank
ZINCZINC000098208342
PDB chain4pzw 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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PDB4pzw Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		Q73 G74 L91 D93 Y132 F169 I171 W176 D289 G291 T292
Binding residue
(residue number reindexed from 1)		Q17 G18 L35 D37 Y76 F113 I115 W120 D227 G229 T230
Annotation score1
Binding affinityMOAD: ic50=0.11uM
PDBbind-CN: -logKd/Ki=6.96,IC50=0.11uM
BindingDB: IC50=20nM
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 D227 T230
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:4pzw, PDBe:4pzw, PDBj:4pzw
PDBsum4pzw
PubMed24780121
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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