Structure of PDB 4di2 Chain A Binding Site BS01

Receptor Information
>4di2 Chain A (length=375) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KKGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAP
HPFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVT
VRANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQT
HVPNLFSLQLCGAASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIV
RVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASST
EKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQ
YLRPVEDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACH
VHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand ID0K9
InChIInChI=1S/C33H44N4O4S/c1-21(40-5)29(39)37-26(16-22-8-6-9-24(14-22)31-34-12-13-42-31)28(38)20-35-27-18-33(10-7-11-33)41-30-25(27)15-23(19-36-30)17-32(2,3)4/h6,8-9,12-15,19,21,26-28,35,38H,7,10-11,16-18,20H2,1-5H3,(H,37,39)/t21-,26+,27+,28-/m1/s1
InChIKeyIUSARDYWEPUTPN-OZBXUNDUSA-N
SMILES
SoftwareSMILES
ACDLabs 12.01O=C(NC(C(O)CNC2c3cc(cnc3OC1(CCC1)C2)CC(C)(C)C)Cc4cccc(c4)c5nccs5)C(OC)C
CACTVS 3.370CO[CH](C)C(=O)N[CH](Cc1cccc(c1)c2sccn2)[CH](O)CN[CH]3CC4(CCC4)Oc5ncc(CC(C)(C)C)cc35
OpenEye OEToolkits 1.7.6C[C@H](C(=O)N[C@@H](Cc1cccc(c1)c2nccs2)[C@@H](CN[C@H]3CC4(CCC4)Oc5c3cc(cn5)CC(C)(C)C)O)OC
CACTVS 3.370CO[C@H](C)C(=O)N[C@@H](Cc1cccc(c1)c2sccn2)[C@H](O)CN[C@H]3CC4(CCC4)Oc5ncc(CC(C)(C)C)cc35
OpenEye OEToolkits 1.7.6CC(C(=O)NC(Cc1cccc(c1)c2nccs2)C(CNC3CC4(CCC4)Oc5c3cc(cn5)CC(C)(C)C)O)OC
FormulaC33 H44 N4 O4 S
Name(2R)-N-{(2S,3R)-4-{[(4'S)-6'-(2,2-dimethylpropyl)-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridin]-4'-yl]amino}-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl}-2-methoxypropanamide
ChEMBLCHEMBL2181911
DrugBank
ZINCZINC000043206371
PDB chain4di2 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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PDB4di2 Design and synthesis of potent, orally efficacious hydroxyethylamine derived beta-site amyloid precursor protein cleaving enzyme (BACE1) inhibitors.
Resolution2.0 Å
Binding residue
(original residue number in PDB)		G11 Q12 G13 L30 D32 G34 P70 Y71 T72 F108 I110 Y198 D228 G230 T329 V332
Binding residue
(residue number reindexed from 1)		G17 Q18 G19 L36 D38 G40 P76 Y77 T78 F114 I116 Y194 D224 G226 T319 V322
Annotation score1
Binding affinityMOAD: ic50=5.5nM
PDBbind-CN: -logKd/Ki=8.26,IC50=5.5nM
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 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:4di2, PDBe:4di2, PDBj:4di2
PDBsum4di2
PubMed22468684
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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