Structure of PDB 2wf1 Chain A Binding Site BS01

Receptor Information
>2wf1 Chain A (length=374) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHPFLHR
YYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPQVTVRANIA
AITESDKFFIQGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHVPNLF
SLQLCGASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRVEINGQ
DLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEKFPDGF
WLGEQLVCWQAGTTPWNIFPVISLYLMGEVTQQSFRITILPQQYLRPVED
VATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACHV
HDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand IDZY1
InChIInChI=1S/C32H38N4O5S/c1-4-24-21-36-13-14-42(39,40)35(2)29-18-25(17-27(24)31(29)36)32(38)34-28(16-22-9-6-5-7-10-22)30(37)20-33-19-23-11-8-12-26(15-23)41-3/h5-12,15,17-18,21,28,30,33,37H,4,13-14,16,19-20H2,1-3H3,(H,34,38)/t28-,30+/m0/s1
InChIKeyMNGUVHPNHVMEDL-MFMCTBQISA-N
SMILES
SoftwareSMILES
ACDLabs 10.04O=C(c2cc3c1n(cc(c1c2)CC)CCS(=O)(=O)N3C)NC(Cc4ccccc4)C(O)CNCc5cccc(OC)c5
OpenEye OEToolkits 1.6.1CCc1cn2c3c1cc(cc3N(S(=O)(=O)CC2)C)C(=O)NC(Cc4ccccc4)C(CNCc5cccc(c5)OC)O
CACTVS 3.352CCc1cn2CC[S](=O)(=O)N(C)c3cc(cc1c23)C(=O)N[CH](Cc4ccccc4)[CH](O)CNCc5cccc(OC)c5
CACTVS 3.352CCc1cn2CC[S](=O)(=O)N(C)c3cc(cc1c23)C(=O)N[C@@H](Cc4ccccc4)[C@H](O)CNCc5cccc(OC)c5
OpenEye OEToolkits 1.6.1CCc1cn2c3c1cc(cc3[N@](S(=O)(=O)CC2)C)C(=O)N[C@@H](Cc4ccccc4)[C@@H](CNCc5cccc(c5)OC)O
FormulaC32 H38 N4 O5 S
NameN-{(1S,2R)-1-benzyl-2-hydroxy-3-[(3-methoxybenzyl)amino]propyl}-7-ethyl-1-methyl-3,4-dihydro-1H-[1,2,5]thiadiazepino[3,4,5-hi]indole-9-carboxamide 2,2-dioxide
ChEMBLCHEMBL539436
DrugBank
ZINCZINC000038998652
PDB chain2wf1 Chain A Residue 2000 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB2wf1 Second Generation of Bace-1 Inhibitors Part 2: Optimisation of the Non-Prime Side Substituent.
Resolution1.6 Å
Binding residue
(original residue number in PDB)		G72 Q73 D93 G95 Y132 T133 Q134 F169 W176 D289 G291 T292 T293 N294 R296 N446
Binding residue
(residue number reindexed from 1)		G11 Q12 D32 G34 Y71 T72 Q73 F108 W115 D217 G219 T220 T221 N222 R224 N374
Annotation score1
Binding affinityMOAD: ic50=0.002uM
PDBbind-CN: -logKd/Ki=8.70,IC50=2nM
BindingDB: IC50=2nM
Enzymatic activity
Catalytic site (original residue number in PDB) D93 S96 N98 A100 Y132 D289 T292
Catalytic site (residue number reindexed from 1) D32 S35 N37 A39 Y71 D217 T220
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:2wf1, PDBe:2wf1, PDBj:2wf1
PDBsum2wf1
PubMed19477642
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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