Structure of PDB 2zdz Chain A Binding Site BS01

Receptor Information
>2zdz Chain A (length=370) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
SFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPF
LHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRA
NIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVP
NLFSLQLCGAGFVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVII
VRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASS
TEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQ
QYLRPCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHD
EFRTAAVEGPFVTLMEDCGY
Ligand information
Ligand ID310
InChIInChI=1S/C27H23ClN4O3/c1-17(33)18-6-10-20(11-7-18)35-21-12-8-19(9-13-21)24-14-15-25(22-4-2-3-5-23(22)28)32(24)16-26(34)31-27(29)30/h2-15H,16H2,1H3,(H4,29,30,31,34)
InChIKeyMIEKBLPHNQZVQQ-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.5.0[H]N=C(N)NC(=O)Cn1c(ccc1c2ccccc2Cl)c3ccc(cc3)Oc4ccc(cc4)C(=O)C
OpenEye OEToolkits 1.5.0[H]/N=C(\N)/NC(=O)Cn1c(ccc1c2ccccc2Cl)c3ccc(cc3)Oc4ccc(cc4)C(=O)C
CACTVS 3.341CC(=O)c1ccc(Oc2ccc(cc2)c3ccc(n3CC(=O)NC(N)=N)c4ccccc4Cl)cc1
ACDLabs 10.04O=C(NC(=[N@H])N)Cn2c(ccc2c1ccccc1Cl)c4ccc(Oc3ccc(C(=O)C)cc3)cc4
FormulaC27 H23 Cl N4 O3
NameN-carbamimidoyl-2-[2-(2-chlorophenyl)-5-[4-(4-ethanoylphenoxy)phenyl]pyrrol-1-yl]ethanamide
ChEMBLCHEMBL253237
DrugBank
ZINCZINC000014962112
PDB chain2zdz Chain A Residue 1 [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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PDB2zdz Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1 and S3 substrate binding pockets.
Resolution2.0 Å
Binding residue
(original residue number in PDB)		G73 Q74 G75 L92 D94 G96 Y133 W138 F170 I172 W177 I180 D290 G292 T294
Binding residue
(residue number reindexed from 1)		G14 Q15 G16 L33 D35 G37 Y74 W79 F111 I113 W118 I121 D225 G227 T229
Annotation score1
Binding affinityMOAD: ic50=0.7uM
PDBbind-CN: -logKd/Ki=6.15,IC50=0.7uM
BindingDB: IC50=700nM
Enzymatic activity
Catalytic site (original residue number in PDB) D94 S97 N99 A101 Y133 D290 T293
Catalytic site (residue number reindexed from 1) D35 S38 N40 A42 Y74 D225 T228
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:2zdz, PDBe:2zdz, PDBj:2zdz
PDBsum2zdz
PubMed18162398
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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