Structure of PDB 4rcd Chain A Binding Site BS01

Receptor Information
>4rcd Chain A (length=368) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGAASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEI
NGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFP
DGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRP
VCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVHDEFRT
AAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID3LL
InChIInChI=1S/C25H19FN4O3/c1-24(12-31-13-24)7-6-15-9-19-22(29-11-15)33-20-5-4-16(17-3-2-8-28-21(17)26)10-18(20)25(19)14-32-23(27)30-25/h2-5,8-11H,12-14H2,1H3,(H2,27,30)/t25-/m0/s1
InChIKeyGKKFBOARESVMBW-VWLOTQADSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CC1(COC1)C#Cc2cnc3Oc4ccc(cc4[C]5(COC(=N5)N)c3c2)c6cccnc6F
OpenEye OEToolkits 1.7.6CC1(COC1)C#Cc2cc3c(nc2)Oc4ccc(cc4C35COC(=N5)N)c6cccnc6F
OpenEye OEToolkits 1.7.6CC1(COC1)C#Cc2cc3c(nc2)Oc4ccc(cc4[C@@]35COC(=N5)N)c6cccnc6F
ACDLabs 12.01Fc1ncccc1c6cc5c(Oc3ncc(C#CC2(C)COC2)cc3C54N=C(OC4)N)cc6
CACTVS 3.385CC1(COC1)C#Cc2cnc3Oc4ccc(cc4[C@@]5(COC(=N5)N)c3c2)c6cccnc6F
FormulaC25 H19 F N4 O3
Name(5S)-7-(2-fluoropyridin-3-yl)-3-[(3-methyloxetan-3-yl)ethynyl]spiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazol]-2'-amine
ChEMBLCHEMBL3359763
DrugBank
ZINCZINC000117741467
PDB chain4rcd Chain A Residue 501 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4rcd Inhibitors of beta-Site Amyloid Precursor Protein Cleaving Enzyme (BACE1): Identification of (S)-7-(2-Fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine (AMG-8718).
Resolution1.9 Å
Binding residue
(original residue number in PDB)		G11 G13 L30 D32 Y71 W76 F108 I118 R128 D228 G230
Binding residue
(residue number reindexed from 1)		G13 G15 L32 D34 Y73 W78 F110 I120 R130 D220 G222
Annotation score1
Binding affinityMOAD: ic50=0.7nM
PDBbind-CN: -logKd/Ki=9.15,IC50=0.7nM
BindingDB: IC50=0.700000nM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
Catalytic site (residue number reindexed from 1) D34 S37 N39 A41 Y73 D220 T223
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:4rcd, PDBe:4rcd, PDBj:4rcd
PDBsum4rcd
PubMed25363711
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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