Structure of PDB 4acx Chain A Binding Site BS01

Receptor Information
>4acx 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]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQD
LKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDGFW
LGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVEDV
ATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHVH
DEFRTAAVEGPFVTLEDCGY
Ligand information
Ligand IDS8Z
InChIInChI=1S/C23H20F4N4O2/c1-32-11-3-5-15-4-2-6-17(12-15)23(16-7-9-18(10-8-16)33-20(24)25)19-29-13-22(26,27)14-31(19)21(28)30-23/h2,4,6-10,12,20H,11,13-14H2,1H3,(H2,28,30)/t23-/m1/s1
InChIKeyDOQWIXXNZSOWDD-HSZRJFAPSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.9.2COCC#Cc1cccc(c1)C2(C3=NCC(CN3C(=N2)N)(F)F)c4ccc(cc4)OC(F)F
OpenEye OEToolkits 1.9.2COCC#Cc1cccc(c1)[C@@]2(C3=NCC(CN3C(=N2)N)(F)F)c4ccc(cc4)OC(F)F
CACTVS 3.385COCC#Cc1cccc(c1)[C]2(N=C(N)N3CC(F)(F)CN=C23)c4ccc(OC(F)F)cc4
CACTVS 3.385COCC#Cc1cccc(c1)[C@]2(N=C(N)N3CC(F)(F)CN=C23)c4ccc(OC(F)F)cc4
ACDLabs 12.01FC(F)Oc1ccc(cc1)C3(N=C(N)N2C3=NCC(F)(F)C2)c4cccc(C#CCOC)c4
FormulaC23 H20 F4 N4 O2
Name(8R)-8-[4-(DIFLUOROMETHOXY)PHENYL]-3,3-DIFLUORO-8-[3-(3-METHOXYPROP-1-YN-1-YL)PHENYL]-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE
ChEMBL
DrugBank
ZINCZINC000073313183
PDB chain4acx Chain A Residue 1504 [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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PDB4acx Aminoimidazoles as BACE-1 inhibitors: the challenge to achieve in vivo brain efficacy.
Resolution2.0 Å
Binding residue
(original residue number in PDB)		Q12 G13 L30 D32 S35 N37 Y71 Q73 W76 F108 I110 I118 R128 D228 G230 T232
Binding residue
(residue number reindexed from 1)		Q14 G15 L32 D34 S37 N39 Y73 Q75 W78 F110 I112 I120 R130 D216 G218 T220
Annotation score1
Binding affinityMOAD: ic50=77.6nM
PDBbind-CN: -logKd/Ki=7.11,IC50=77.6nM
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 D216 T219
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:4acx, PDBe:4acx, PDBj:4acx
PDBsum4acx
PubMed22325942
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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