Structure of PDB 2ph8 Chain A Binding Site BS01

Receptor Information
>2ph8 Chain A (length=365) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGAWAGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEING
QDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDG
FWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYLRPVS
QDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACFRTAAV
EGPFVTLDMEDCGYN
Ligand information
Ligand ID35A
InChIInChI=1S/C24H33N3O4S/c1-17-8-10-18-6-5-7-19(12-18)15-24(2,25)23(28)31-16-20-13-21(11-9-17)26-22(14-20)27(3)32(4,29)30/h5-7,12-14,17H,8-11,15-16,25H2,1-4H3/t17-,24-/m1/s1
InChIKeyQWDOKZPZLWNULU-MZNJEOGPSA-N
SMILES
SoftwareSMILES
CACTVS 3.341C[CH]1CCc2cccc(C[C](C)(N)C(=O)OCc3cc(CC1)nc(c3)N(C)[S](C)(=O)=O)c2
ACDLabs 10.04O=S(=O)(N(c1nc3cc(c1)COC(=O)C(N)(C)Cc2cccc(c2)CCC(CC3)C)C)C
CACTVS 3.341C[C@@H]1CCc2cccc(C[C@@](C)(N)C(=O)OCc3cc(CC1)nc(c3)N(C)[S](C)(=O)=O)c2
OpenEye OEToolkits 1.5.0C[C@@H]1CCc2cccc(c2)C[C@@](C(=O)OCc3cc(nc(c3)[N@](C)S(=O)(=O)C)CC1)(C)N
OpenEye OEToolkits 1.5.0CC1CCc2cccc(c2)CC(C(=O)OCc3cc(nc(c3)N(C)S(=O)(=O)C)CC1)(C)N
FormulaC24 H33 N3 O4 S
NameN-[(5R,14R)-5-AMINO-5,14-DIMETHYL-4-OXO-3-OXA-18-AZATRICYCLO[15.3.1.1~7,11~]DOCOSA-1(21),7(22),8,10,17,19-HEXAEN-19-YL]-N-METHYLMETHANESULFONAMIDE
ChEMBL
DrugBankDB07019
ZINCZINC000016052369
PDB chain2ph8 Chain A Residue 388 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB2ph8 Strategies toward improving the brain penetration of macrocyclic tertiary carbinamine BACE-1 inhibitors.
Resolution1.7 Å
Binding residue
(original residue number in PDB)		L30 D32 G34 Y71 T72 Q73 D228 G230 T231 T232 N233 R235
Binding residue
(residue number reindexed from 1)		L34 D36 G38 Y75 T76 Q77 D218 G220 T221 T222 N223 R225
Annotation score1
Binding affinityMOAD: ic50=1800nM
PDBbind-CN: -logKd/Ki=5.74,IC50=1800nM
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 D218 T221
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:2ph8, PDBe:2ph8, PDBj:2ph8
PDBsum2ph8
PubMed17827011
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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