Structure of PDB 4h3j Chain A Binding Site BS01

Receptor Information
>4h3j Chain A (length=390) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
GSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPHP
FLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTVR
ANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTHV
PNLFSLQLCGAGFPLNQSEVLASVGGSMIIGGIDHSLYTGSLWYTPIRRE
WYYEVIIVRVEINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVK
SIKAASSTEKFPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSF
RITILPQQYLRPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFD
RARKRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNI
Ligand information
Ligand ID10W
InChIInChI=1S/C24H20FN5OS/c1-29-22(31)18-13-30(17-5-3-2-4-6-17)14-24(18,28-23(29)27)21-10-9-20(32-21)15-7-8-19(25)16(11-15)12-26/h2-11,18H,13-14H2,1H3,(H2,27,28)/t18-,24-/m0/s1
InChIKeyDWVJKKOFIHHAKC-UUOWRZLLSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CN1C(=O)C2CN(CC2(NC1=N)c3ccc(s3)c4ccc(c(c4)C#N)F)c5ccccc5
ACDLabs 12.01Fc5ccc(c1sc(cc1)C42NC(=[N@H])N(C(=O)C2CN(c3ccccc3)C4)C)cc5C#N
OpenEye OEToolkits 1.7.6[H]/N=C/1\N[C@]2(CN(C[C@H]2C(=O)N1C)c3ccccc3)c4ccc(s4)c5ccc(c(c5)C#N)F
CACTVS 3.370CN1C(=N)N[C]2(CN(C[CH]2C1=O)c3ccccc3)c4sc(cc4)c5ccc(F)c(c5)C#N
CACTVS 3.370CN1C(=N)N[C@]2(CN(C[C@H]2C1=O)c3ccccc3)c4sc(cc4)c5ccc(F)c(c5)C#N
FormulaC24 H20 F N5 O S
Name2-fluoro-5-{5-[(2E,4aR,7aR)-2-imino-3-methyl-4-oxo-6-phenyloctahydro-7aH-pyrrolo[3,4-d]pyrimidin-7a-yl]thiophen-2-yl}benzonitrile
ChEMBLCHEMBL2178148
DrugBank
ZINCZINC000034787398
PDB chain4h3j Chain A Residue 502 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
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PDB4h3j Design and Validation of Bicyclic Iminopyrimidinones As Beta Amyloid Cleaving Enzyme-1 (BACE1) Inhibitors: Conformational Constraint to Favor a Bioactive Conformation.
Resolution1.6 Å
Binding residue
(original residue number in PDB)		G72 Q73 G74 D93 S96 N98 V130 T133 Q134 I179 R189 D289 G291
Binding residue
(residue number reindexed from 1)		G15 Q16 G17 D36 S39 N41 V73 T76 Q77 I122 R132 D232 G234
Annotation score1
Binding affinityMOAD: Ki=90nM
PDBbind-CN: -logKd/Ki=7.05,Ki=90nM
Enzymatic activity
Catalytic site (original residue number in PDB) D93 S96 N98 A100 Y132 D289 T292
Catalytic site (residue number reindexed from 1) D36 S39 N41 A43 Y75 D232 T235
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:4h3j, PDBe:4h3j, PDBj:4h3j
PDBsum4h3j
PubMed22989333
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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