Structure of PDB 5he5 Chain A Binding Site BS01

Receptor Information
>5he5 Chain A (length=387) 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
RITILPQQYLRPVEDSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRAR
KRIGFAVSACHVHDEFRTAAVEGPFVTLDMEDCGYNI
Ligand information
Ligand ID60S
InChIInChI=1S/C18H19FN8OS/c1-9-13(19)14(22-2)24-17(23-9)27-7-11-15(28)26(3)16(21)25-18(11,8-27)12-5-4-10(6-20)29-12/h4-5,11H,7-8H2,1-3H3,(H2,21,25)(H,22,23,24)/t11-,18-/m0/s1
InChIKeyZGUINBOSNMEMBB-VOJFVSQTSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CNc1nc(nc(C)c1F)N2C[CH]3C(=O)N(C)C(=N)N[C]3(C2)c4sc(cc4)C#N
ACDLabs 12.01C32(C(CN(c1nc(NC)c(F)c(n1)C)C2)C(=O)N(\C(=N)N3)C)c4sc(cc4)C#N
OpenEye OEToolkits 2.0.4Cc1c(c(nc(n1)N2CC3C(=O)N(C(=N)NC3(C2)c4ccc(s4)C#N)C)NC)F
OpenEye OEToolkits 2.0.4[H]/N=C/1\N[C@]2(CN(C[C@H]2C(=O)N1C)c3nc(c(c(n3)NC)F)C)c4ccc(s4)C#N
CACTVS 3.385CNc1nc(nc(C)c1F)N2C[C@H]3C(=O)N(C)C(=N)N[C@]3(C2)c4sc(cc4)C#N
FormulaC18 H19 F N8 O S
Name5-{(2E,4aR,7aR)-6-[5-fluoro-4-methyl-6-(methylamino)pyrimidin-2-yl]-2-imino-3-methyl-4-oxooctahydro-7aH-pyrrolo[3,4-d]pyrimidin-7a-yl}thiophene-2-carbonitrile
ChEMBLCHEMBL3799879
DrugBank
ZINCZINC000584905342
PDB chain5he5 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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PDB5he5 Structure-Based Design of an Iminoheterocyclic beta-Site Amyloid Precursor Protein Cleaving Enzyme (BACE) Inhibitor that Lowers Central A beta in Nonhuman Primates.
Resolution1.55 Å
Binding residue
(original residue number in PDB)		L91 D93 S96 V130 Y132 F169 W176 R189 D289 G291
Binding residue
(residue number reindexed from 1)		L34 D36 S39 V73 Y75 F112 W119 R132 D232 G234
Annotation score1
Binding affinityMOAD: Ki=336nM
PDBbind-CN: -logKd/Ki=6.47,Ki=336nM
BindingDB: IC50=157nM,Ki=336nM
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:5he5, PDBe:5he5, PDBj:5he5
PDBsum5he5
PubMed26937601
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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