Structure of PDB 6jt3 Chain A Binding Site BS01

Receptor Information
>6jt3 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]
RGSFVEMVDNLRGKSGQGYYVEMTVGSPPQTLNILVDTGSSNFAVGAAPH
PFLHRYYQRQLSSTYRDLRKGVYVPYTQGKWEGELGTDLVSIPHGPNVTV
RANIAAITESDKFFINGSNWEGILGLAYAEIARPDDSLEPFFDSLVKQTH
VPNLFSLQLCGASVGGSMIIGGIDHSLYTGSLWYTPIRREWYYEVIIVRV
EINGQDLKMDCKEYNYDKSIVDSGTTNLRLPKKVFEAAVKSIKAASSTEK
FPDGFWLGEQLVCWQAGTTPWNIFPVISLYLMGEVTNQSFRITILPQQYL
RPVEDVATSQDDCYKFAISQSSTGTVMGAVIMEGFYVVFDRARKRIGFAV
SACHVHDEFRTAAVEGPFVTLDMEDCGYN
Ligand information
Ligand IDC83
InChIInChI=1S/C18H18F3N5O2S/c1-9-15(21)18(2,26-17(22)29-9)11-5-10(3-4-12(11)20)25-16(27)13-6-24-14(7-23-13)28-8-19/h3-7,9,15H,8H2,1-2H3,(H2,22,26)(H,25,27)/t9-,15+,18-/m1/s1
InChIKeyJWJQXZNLFNMIHE-AHRODOEDSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.6CC1C(C(N=C(S1)N)(C)c2cc(ccc2F)NC(=O)c3cnc(cn3)OCF)F
CACTVS 3.385C[C@H]1SC(=N[C@@](C)([C@H]1F)c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)N
OpenEye OEToolkits 2.0.6C[C@@H]1[C@@H]([C@@](N=C(S1)N)(C)c2cc(ccc2F)NC(=O)c3cnc(cn3)OCF)F
CACTVS 3.385C[CH]1SC(=N[C](C)([CH]1F)c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)N
FormulaC18 H18 F3 N5 O2 S
NameN-[3-[(4R,5R,6R)-2-azanyl-5-fluoranyl-4,6-dimethyl-5,6-dihydro-1,3-thiazin-4-yl]-4-fluoranyl-phenyl]-5-(fluoranylmethoxy)pyrazine-2-carboxamide
ChEMBLCHEMBL4557670
DrugBank
ZINC
PDB chain6jt3 Chain A Residue 505 [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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PDB6jt3 Discovery of an Extremely Potent Thiazine-Based beta-Secretase Inhibitor with Reduced Cardiovascular and Liver Toxicity at a Low Projected Human Dose.
Resolution2.4 Å
Binding residue
(original residue number in PDB)		G11 Q12 G13 L30 D32 Y71 F108 I118 D228 G230 T231 T232 A335
Binding residue
(residue number reindexed from 1)		G16 Q17 G18 L35 D37 Y76 F113 I123 D222 G224 T225 T226 A329
Annotation score1
Binding affinityMOAD: ic50=5nM
PDBbind-CN: -logKd/Ki=8.30,IC50=5.0nM
BindingDB: IC50=0.380000nM
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:6jt3, PDBe:6jt3, PDBj:6jt3
PDBsum6jt3
PubMed31549838
UniProtP56817|BACE1_HUMAN Beta-secretase 1 (Gene Name=BACE1)

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