Structure of PDB 5ls6 Chain A Binding Site BS10

Receptor Information
>5ls6 Chain A (length=570) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
KGPVCWRKRVKSEYMRLRQLKRFRRADEVKSMFSSNRQKILERTEILNQE
WKQRRIQPVHILTSVSSLRGTRECSVTSDLDFPTQVIPLKTLNAVASVPI
MYSWSPLQQNFMVEDETVLHNIPYMGDEVLDQDGTFIEELIKNYDGKVHG
DRECGFINDEIFVELVNALGQYNESRPPRSDKIFEAISSMFPDKGTAEEL
KEKYKELTQPPECTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFLH
PFHATPNTYKRKNTETALDNKPCGPQCYQHLEGAKEFAAALTAERIKTPN
IEPPENVEWSGAEASMFRVLIGTYYDNFCAIARLIGTKTCRQVYEFRVKE
SSIIAPAHVYNYQPCDHPRQPCDSSCPCVIAQNFCEKFCQCSSECQNRFP
GCRCKAQCNTKQCPCYLAVRECDPDLCLTCGAADHWDSKNVSCKNCSIQR
GSKKHLLLAPSDVAGWGIFIKDPVQKNEFISEYCGEIISQDEADRRGKVY
DKYMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRI
GIFAKRAIQTGEELFFDYRY
Ligand information
Ligand ID74D
InChIInChI=1S/C28H36F2N4O3/c1-17-14-24(37-5)22(26(35)32-17)15-31-27(36)25-19(3)34(23-9-7-6-8-21(23)25)18(2)20-10-12-33(13-11-20)16-28(4,29)30/h6-9,14,18,20,22H,10-13,15-16H2,1-5H3,(H,31,36)/t18-,22+/m1/s1
InChIKeyMNZANYNOXFULDI-GCJKJVERSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 2.0.5Cc1c(c2ccccc2n1C(C)C3CCN(CC3)CC(C)(F)F)C(=O)NCC4C(=CC(=NC4=O)C)OC
CACTVS 3.385COC1=CC(=NC(=O)[CH]1CNC(=O)c2c(C)n([CH](C)C3CCN(CC3)CC(C)(F)F)c4ccccc24)C
CACTVS 3.385COC1=CC(=NC(=O)[C@H]1CNC(=O)c2c(C)n([C@H](C)C3CCN(CC3)CC(C)(F)F)c4ccccc24)C
OpenEye OEToolkits 2.0.5Cc1c(c2ccccc2n1[C@H](C)C3CCN(CC3)CC(C)(F)F)C(=O)NCC4C(=CC(=NC4=O)C)OC
FormulaC28 H36 F2 N4 O3
Name1-[(1~{R})-1-[1-[2,2-bis(fluoranyl)propyl]piperidin-4-yl]ethyl]-~{N}-[(4-methoxy-6-methyl-2-oxidanylidene-3~{H}-pyridin-3-yl)methyl]-2-methyl-indole-3-carboxamide
ChEMBL
DrugBank
ZINCZINC000584905089
PDB chain5ls6 Chain A Residue 809 [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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PDB5ls6 Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-Cell Lymphomas.
Resolution3.47 Å
Binding residue
(original residue number in PDB)		Y111 W624 Y661 C663 F665 F686 N688
Binding residue
(residue number reindexed from 1)		Y102 W466 Y503 C505 F507 F528 N530
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=9.00,IC50<0.001uM
Enzymatic activity
Enzyme Commision number 2.1.1.356: [histone H3]-lysine(27) N-trimethyltransferase.
Gene Ontology
Molecular Function
GO:0042054 histone methyltransferase activity
GO:0046976 histone H3K27 methyltransferase activity
Biological Process
GO:0006338 chromatin remodeling

View graph for
Molecular Function
View graph for
Biological Process
External links
PDB RCSB:5ls6, PDBe:5ls6, PDBj:5ls6
PDBsum5ls6
PubMed27739677
UniProtQ15910|EZH2_HUMAN Histone-lysine N-methyltransferase EZH2 (Gene Name=EZH2)

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