Structure of PDB 2vnn Chain A Binding Site BS01

Receptor Information
>2vnn 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 IDCM7
InChIInChI=1S/C32H35F3N4O4S/c1-3-23-20-39-12-13-44(42,43)38(2)28-17-24(16-26(23)30(28)39)31(41)37-27(15-21-8-5-4-6-9-21)29(40)19-36-18-22-10-7-11-25(14-22)32(33,34)35/h4-11,14,16-17,20,27,29,36,40H,3,12-13,15,18-19H2,1-2H3,(H,37,41)/t27-,29+/m0/s1
InChIKeyMSHYGGHZTGSTOG-LMSSTIIKSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.5.0CCc1cn2c3c1cc(cc3[N@@](S(=O)(=O)CC2)C)C(=O)N[C@@H](Cc4ccccc4)[C@@H](CNCc5cccc(c5)C(F)(F)F)O
ACDLabs 10.04FC(F)(F)c1cccc(c1)CNCC(O)C(NC(=O)c3cc4c2n(cc(c2c3)CC)CCS(=O)(=O)N4C)Cc5ccccc5
CACTVS 3.341CCc1cn2CC[S](=O)(=O)N(C)c3cc(cc1c23)C(=O)N[CH](Cc4ccccc4)[CH](O)CNCc5cccc(c5)C(F)(F)F
CACTVS 3.341CCc1cn2CC[S](=O)(=O)N(C)c3cc(cc1c23)C(=O)N[C@@H](Cc4ccccc4)[C@H](O)CNCc5cccc(c5)C(F)(F)F
OpenEye OEToolkits 1.5.0CCc1cn2c3c1cc(cc3N(S(=O)(=O)CC2)C)C(=O)NC(Cc4ccccc4)C(CNCc5cccc(c5)C(F)(F)F)O
FormulaC32 H35 F3 N4 O4 S
NameN-[(1S,2R)-1-benzyl-2-hydroxy-3-{[3-(trifluoromethyl)benzyl]amino}propyl]-7-ethyl-1-methyl-3,4-dihydro-1H-[1,2,5]thiadiazepino[3,4,5-hi]indole-9-carboxamide 2,2-dioxide
ChEMBLCHEMBL554349
DrugBank
ZINCZINC000016052623
PDB chain2vnn Chain A Residue 2000 [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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PDB2vnn Second Generation of Hydroxyethylamine Bace-1 Inhibitors: Optimizing Potency and Oral Bioavailability.
Resolution1.87 Å
Binding residue
(original residue number in PDB)		G72 L91 D93 G95 S96 Y132 T133 Q134 F169 W176 Y259 D289 G291 T292 T293 N294 R296 N446
Binding residue
(residue number reindexed from 1)		G11 L30 D32 G34 S35 Y71 T72 Q73 F108 W115 Y187 D217 G219 T220 T221 N222 R224 N374
Annotation score1
Binding affinityMOAD: ic50=2nM
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:2vnn, PDBe:2vnn, PDBj:2vnn
PDBsum2vnn
PubMed18457381
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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