Structure of PDB 4zpe Chain A Binding Site BS01

Receptor Information
>4zpe Chain A (length=369) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGAWAGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEIN
GQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPD
GFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPV
ESQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACDEFR
TAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID4QA
InChIInChI=1S/C29H37FN4O2/c1-21(2)36-26-13-6-8-22(18-26)20-33-16-14-29(15-17-33)27(31-24-10-4-3-5-11-24)32-28(35)34(29)25-12-7-9-23(30)19-25/h6-9,12-13,18-19,21,24H,3-5,10-11,14-17,20H2,1-2H3,(H,31,32,35)
InChIKeyKZMSAJWZLCSCQP-UHFFFAOYSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.9.2CC(C)Oc1cccc(c1)CN2CCC3(CC2)C(=NC(=O)N3c4cccc(c4)F)NC5CCCCC5
CACTVS 3.385CC(C)Oc1cccc(CN2CCC3(CC2)N(C(=O)N=C3NC4CCCCC4)c5cccc(F)c5)c1
ACDLabs 12.01C24(CCN(Cc1cc(ccc1)OC(C)C)CC2)C(NC3CCCCC3)=NC(N4c5cccc(c5)F)=O
FormulaC29 H37 F N4 O2
Name4-(cyclohexylamino)-1-(3-fluorophenyl)-8-[3-(propan-2-yloxy)benzyl]-1,3,8-triazaspiro[4.5]dec-3-en-2-one
ChEMBL
DrugBank
ZINCZINC000114169955
PDB chain4zpe Chain A Residue 501 [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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PDB4zpe Methyl-substitution of an iminohydantoin spiropiperidine beta-secretase (BACE-1) inhibitor has a profound effect on its potency.
Resolution1.7 Å
Binding residue
(original residue number in PDB)		L30 Y71 T72 Q73 G74 F108 I110 W115 Y198 G230
Binding residue
(residue number reindexed from 1)		L34 Y75 T76 Q77 G78 F112 I114 W119 Y189 G221
Annotation score1
Binding affinityMOAD: ic50=0.45uM
PDBbind-CN: -logKd/Ki=6.35,IC50=0.45uM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
Catalytic site (residue number reindexed from 1) D36 S39 N41 A43 Y75 D219 T222
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:4zpe, PDBe:4zpe, PDBj:4zpe
PDBsum4zpe
PubMed26195137
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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