Structure of PDB 2qzl Chain A Binding Site BS01

Receptor Information
>2qzl 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]
RGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPH
PFLHRYYQRQLSSTYRDLRKGVYVPYTQGAWAGELGTDLVSIPHGPNVTV
RANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTH
VPNLFSLQLCGASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVESQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAVSACH
VHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand IDIXS
InChIInChI=1S/C34H44FN5O5S/c1-22(2)20-37-32(41)24(4)36-21-30(16-25-10-8-7-9-11-25)39-34(43)28-17-27(18-31(19-28)40(5)46(6,44)45)33(42)38-23(3)26-12-14-29(35)15-13-26/h7-15,17-19,22-24,30,36H,16,20-21H2,1-6H3,(H,37,41)(H,38,42)(H,39,43)/t23-,24+,30+/m1/s1
InChIKeyFZTXBRKPIRTQCY-QEGDFHJFSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.5.0CC(C)CNC(=O)C(C)NCC(Cc1ccccc1)NC(=O)c2cc(cc(c2)N(C)S(=O)(=O)C)C(=O)NC(C)c3ccc(cc3)F
CACTVS 3.341CC(C)CNC(=O)[CH](C)NC[CH](Cc1ccccc1)NC(=O)c2cc(cc(c2)C(=O)N[CH](C)c3ccc(F)cc3)N(C)[S](C)(=O)=O
OpenEye OEToolkits 1.5.0CC(C)CNC(=O)[C@H](C)NC[C@H](Cc1ccccc1)NC(=O)c2cc(cc(c2)N(C)S(=O)(=O)C)C(=O)N[C@H](C)c3ccc(cc3)F
ACDLabs 10.04O=S(=O)(N(c1cc(cc(c1)C(=O)NC(c2ccc(F)cc2)C)C(=O)NC(Cc3ccccc3)CNC(C(=O)NCC(C)C)C)C)C
CACTVS 3.341CC(C)CNC(=O)[C@H](C)NC[C@H](Cc1ccccc1)NC(=O)c2cc(cc(c2)C(=O)N[C@H](C)c3ccc(F)cc3)N(C)[S](C)(=O)=O
FormulaC34 H44 F N5 O5 S
NameN-[(1S)-1-benzyl-2-{[(1S)-2-(isobutylamino)-1-methyl-2-oxoethyl]amino}ethyl]-N'-[(1R)-1-(4-fluorophenyl)ethyl]-5-[methyl(methylsulfonyl)amino]isophthalamide
ChEMBLCHEMBL379513
DrugBank
ZINCZINC000024926684
PDB chain2qzl Chain A Residue 449 [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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PDB2qzl BACE-1 inhibition by a series of psi[CH2NH] reduced amide isosteres
Resolution1.8 Å
Binding residue
(original residue number in PDB)		G11 Q12 G13 Y14 L30 D32 G34 Y71 T72 Q73 F108 W115 D228 G230 T231 T232 N233 R235 A335
Binding residue
(residue number reindexed from 1)		G16 Q17 G18 Y19 L35 D37 G39 Y76 T77 Q78 F113 W120 D222 G224 T225 T226 N227 R229 A325
Annotation score1
Binding affinityMOAD: ic50=8nM
PDBbind-CN: -logKd/Ki=8.10,IC50=8nM
BindingDB: IC50=8nM
Enzymatic activity
Catalytic site (original residue number in PDB) D32 S35 N37 A39 Y71 D228 T231
Catalytic site (residue number reindexed from 1) D37 S40 N42 A44 Y76 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:2qzl, PDBe:2qzl, PDBj:2qzl
PDBsum2qzl
PubMed16690314
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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