Structure of PDB 2p8h Chain A Binding Site BS01

Receptor Information
>2p8h Chain A (length=379) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
RRGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAP
HPFLHRYYQRQLSSTYRDLRKGVYVPYTQGAWAGELGTDLVSIPHGPNVT
VRANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQT
HVPNLFSLQLCGAVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAV
SACHVHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand IDMY9
InChIInChI=1S/C33H40FN5O6S/c1-20(22-12-14-25(34)15-13-22)35-30(41)23-17-24(19-26(18-23)39(5)46(6,44)45)31(42)36-27(16-21-10-8-7-9-11-21)29(40)28-32(43)38(4)33(2,3)37-28/h7-15,17-20,27-29,37,40H,16H2,1-6H3,(H,35,41)(H,36,42)/t20-,27+,28+,29+/m1/s1
InChIKeyYNXGIROKYOHHJW-UFAZYNLISA-N
SMILES
SoftwareSMILES
CACTVS 3.341C[CH](NC(=O)c1cc(cc(c1)C(=O)N[CH](Cc2ccccc2)[CH](O)[CH]3NC(C)(C)N(C)C3=O)N(C)[S](C)(=O)=O)c4ccc(F)cc4
CACTVS 3.341C[C@@H](NC(=O)c1cc(cc(c1)C(=O)N[C@@H](Cc2ccccc2)[C@H](O)[C@@H]3NC(C)(C)N(C)C3=O)N(C)[S](C)(=O)=O)c4ccc(F)cc4
OpenEye OEToolkits 1.5.0C[C@H](c1ccc(cc1)F)NC(=O)c2cc(cc(c2)N(C)S(=O)(=O)C)C(=O)N[C@@H](Cc3ccccc3)[C@@H]([C@H]4C(=O)N(C(N4)(C)C)C)O
ACDLabs 10.04O=C1N(C)C(NC1C(O)C(NC(=O)c3cc(N(C)S(=O)(=O)C)cc(C(=O)NC(c2ccc(F)cc2)C)c3)Cc4ccccc4)(C)C
OpenEye OEToolkits 1.5.0CC(c1ccc(cc1)F)NC(=O)c2cc(cc(c2)N(C)S(=O)(=O)C)C(=O)NC(Cc3ccccc3)C(C4C(=O)N(C(N4)(C)C)C)O
FormulaC33 H40 F N5 O6 S
NameN-{(1S,2S)-1-BENZYL-2-HYDROXY-2-[(4S)-1,2,2-TRIMETHYL-5-OXOIMIDAZOLIDIN-4-YL]ETHYL}-N'-[(1R)-1-(4-FLUOROPHENYL)ETHYL]-5-[METHYL(METHYLSULFONYL)AMINO]ISOPHTHALAMIDE
ChEMBLCHEMBL1234552
DrugBank
ZINCZINC000024819433
PDB chain2p8h Chain A Residue 386 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB2p8h Design and Synthesis of 2,3,5-Substituted Imidazolidin-4-one Inhibitors of BACE-1.
Resolution1.8 Å
Binding residue
(original residue number in PDB)		G11 Q12 G13 Y14 L30 D32 G34 Y71 T72 Q73 F108 W115 Y198 D228 S229 G230 T232 N233 R235 A335
Binding residue
(residue number reindexed from 1)		G17 Q18 G19 Y20 L36 D38 G40 Y77 T78 Q79 F114 W121 Y192 D222 S223 G224 T226 N227 R229 A329
Annotation score1
Binding affinityMOAD: ic50=71nM
PDBbind-CN: -logKd/Ki=7.15,IC50=71nM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
Catalytic site (residue number reindexed from 1) D38 S41 N43 A45 Y77 D222 T225
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:2p8h, PDBe:2p8h, PDBj:2p8h
PDBsum2p8h
PubMed17458843
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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