Structure of PDB 4fm8 Chain A Binding Site BS01

Receptor Information
>4fm8 Chain A (length=394) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
FVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFL
HRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVRAN
IAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPN
LFSLQLCGASEVLASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIV
RVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASST
EKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQ
YLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGF
AVSACHVHDEFRTAAVEGPFVTLDMEDCGYNIPQTDESRSHHHH
Ligand information
Ligand ID0UQ
InChIInChI=1S/C24H32FN3O3S/c1-18(2)31-23-10-5-7-20(13-23)16-27-12-11-24(15-19(27)3)17-26(4)32(29,30)28(24)22-9-6-8-21(25)14-22/h5-10,13-14,18-19H,11-12,15-17H2,1-4H3/t19-,24+/m0/s1
InChIKeyCVPXZTQJPHYLAQ-YADARESESA-N
SMILES
SoftwareSMILES
CACTVS 3.370CC(C)Oc1cccc(CN2CC[C]3(C[CH]2C)CN(C)[S](=O)(=O)N3c4cccc(F)c4)c1
CACTVS 3.370CC(C)Oc1cccc(CN2CC[C@@]3(C[C@@H]2C)CN(C)[S](=O)(=O)N3c4cccc(F)c4)c1
OpenEye OEToolkits 1.7.6C[C@H]1C[C@]2(CCN1Cc3cccc(c3)OC(C)C)CN(S(=O)(=O)N2c4cccc(c4)F)C
OpenEye OEToolkits 1.7.6CC1CC2(CCN1Cc3cccc(c3)OC(C)C)CN(S(=O)(=O)N2c4cccc(c4)F)C
ACDLabs 12.01Fc4cccc(N3C1(CCN(C(C)C1)Cc2cccc(OC(C)C)c2)CN(C)S3(=O)=O)c4
FormulaC24 H32 F N3 O3 S
Name(5R,7S)-1-(3-fluorophenyl)-3,7-dimethyl-8-[3-(propan-2-yloxy)benzyl]-2-thia-1,3,8-triazaspiro[4.5]decane 2,2-dioxide
ChEMBLCHEMBL2177473
DrugBank
ZINCZINC000068153166
PDB chain4fm8 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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PDB4fm8 Spirocyclic sulfamides as beta-secretase 1 (BACE-1) inhibitors for the treatment of Alzheimer's disease: utilization of structure based drug design, WaterMap, and CNS penetration studies to identify centrally efficacious inhibitors.
Resolution1.9 Å
Binding residue
(original residue number in PDB)		Q12 G13 L30 D32 Y71 Q73 G74 F108 I110 W115 G230
Binding residue
(residue number reindexed from 1)		Q14 G15 L32 D34 Y73 Q75 G76 F110 I112 W117 G226
Annotation score1
Binding affinityMOAD: ic50=2.4uM
PDBbind-CN: -logKd/Ki=5.97,Kd=1.06uM
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 D224 T227
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:4fm8, PDBe:4fm8, PDBj:4fm8
PDBsum4fm8
PubMed22984865
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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