Structure of PDB 4zpf Chain A Binding Site BS01

Receptor Information
>4zpf Chain A (length=371) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGAWAGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVE
INGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKF
PDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLR
PVSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHDE
FRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID4QD
InChIInChI=1S/C29H38FN5O2/c1-21(19-31)37-26-12-5-7-22(17-26)20-34-15-13-29(14-16-34)27(32-24-9-3-2-4-10-24)33-28(36)35(29)25-11-6-8-23(30)18-25/h5-8,11-12,17-18,21,24H,2-4,9-10,13-16,19-20,31H2,1H3,(H,32,33,36)/t21-/m0/s1
InChIKeyGJCCGBZILLQLCV-NRFANRHFSA-N
SMILES
SoftwareSMILES
CACTVS 3.385C[C@@H](CN)Oc1cccc(CN2CCC3(CC2)N(C(=O)N=C3NC4CCCCC4)c5cccc(F)c5)c1
OpenEye OEToolkits 1.9.2CC(CN)Oc1cccc(c1)CN2CCC3(CC2)C(=NC(=O)N3c4cccc(c4)F)NC5CCCCC5
CACTVS 3.385C[CH](CN)Oc1cccc(CN2CCC3(CC2)N(C(=O)N=C3NC4CCCCC4)c5cccc(F)c5)c1
OpenEye OEToolkits 1.9.2C[C@@H](CN)Oc1cccc(c1)CN2CCC3(CC2)C(=NC(=O)N3c4cccc(c4)F)NC5CCCCC5
ACDLabs 12.01C23(CCN(Cc1cc(ccc1)OC(C)CN)CC2)N(C(N=C3NC4CCCCC4)=O)c5cccc(c5)F
FormulaC29 H38 F N5 O2
Name8-(3-{[(2S)-1-aminopropan-2-yl]oxy}benzyl)-4-(cyclohexylamino)-1-(3-fluorophenyl)-1,3,8-triazaspiro[4.5]dec-3-en-2-one
ChEMBL
DrugBank
ZINCZINC000114171252
PDB chain4zpf 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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PDB4zpf Methyl-substitution of an iminohydantoin spiropiperidine beta-secretase (BACE-1) inhibitor has a profound effect on its potency.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		Q12 G13 L30 D32 Y71 T72 Q73 F108 I110 W115 G230
Binding residue
(residue number reindexed from 1)		Q16 G17 L34 D36 Y75 T76 Q77 F112 I114 W119 G223
Annotation score1
Binding affinityMOAD: ic50=0.18uM
PDBbind-CN: -logKd/Ki=6.74,IC50=0.18uM
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 D221 T224
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:4zpf, PDBe:4zpf, PDBj:4zpf
PDBsum4zpf
PubMed26195137
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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