Structure of PDB 4x61 Chain A Binding Site BS02

Receptor Information
>4x61 Chain A (length=625) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
RVSSGRDLNCVPEIADTLGAVAKQGFDFLCMPVFHPRFKREFIQEPAKNR
PGPQTRSDLLLSGRDWNTLIVGKLSPWIRPDSKVEKIRRNSEAAMLQELN
FGAYLGLPAFLLPLNQEDNTNLARVLTNHIHTGHHSSMFWMRVPLVAPED
LRDDIIENAPTTHTEEYSGEEKTWMWWHNFRTLCDYSKRIAVALEIGADL
PSNHVIDRWLGEPIKAAILPTSIFLTNKKGFPVLSKMHQRLIFRLLKLEV
QFIITGTNHHSEKEFCSYLQYLEYLSQNRPPPNAYELFAKGYEDYLQSPL
QPLMDNLESQTYEVFEKDPIKYSQYQQAIYKCLLDRVPEEEKDTNVQVLM
VLGAGRGPLVNASLRAAKQADRRIKLYAVEKNPNAVVTLENWQFEEWGSQ
VTVVSSDMREWVAPEKADIIVSELLGSFADNELSPECLDGAQHFLKDDGV
SIPGEYTSFLAPISSSKLYNEVRACREKDRDPEAQFEMPYVVRLHNFHQL
SAPQPCFTFSHPNRDPMIDNNRYCTLEFPVEVNTVLHGFAGYFETVLYQD
ITLSIRPETHSPGMFSWFPILFPIKQPITVREGQTICVRFWRCSNSKKVW
YEWAVTAPVCSAIHNPTGRSYTIGL
Ligand information
Ligand ID3XV
InChIInChI=1S/C20H25N5O3/c26-17(10-25-6-5-14-3-1-2-4-15(14)9-25)8-21-20(27)18-7-19(23-13-22-18)24-16-11-28-12-16/h1-4,7,13,16-17,26H,5-6,8-12H2,(H,21,27)(H,22,23,24)/t17-/m0/s1
InChIKeyZKXZLIFRWWKZRY-KRWDZBQOSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.9.2c1ccc2c(c1)CCN(C2)C[C@H](CNC(=O)c3cc(ncn3)NC4COC4)O
CACTVS 3.385O[CH](CNC(=O)c1cc(NC2COC2)ncn1)CN3CCc4ccccc4C3
ACDLabs 12.01O=C(NCC(O)CN2Cc1ccccc1CC2)c4ncnc(NC3COC3)c4
OpenEye OEToolkits 1.9.2c1ccc2c(c1)CCN(C2)CC(CNC(=O)c3cc(ncn3)NC4COC4)O
CACTVS 3.385O[C@@H](CNC(=O)c1cc(NC2COC2)ncn1)CN3CCc4ccccc4C3
FormulaC20 H25 N5 O3
NameN-[(2S)-3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl]-6-(oxetan-3-ylamino)pyrimidine-4-carboxamide
ChEMBLCHEMBL4060831
DrugBank
ZINCZINC000220110600
PDB chain4x61 Chain A Residue 702 [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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PDB4x61 A selective inhibitor of PRMT5 with in vivo and in vitro potency in MCL models.
Resolution2.85 Å
Binding residue
(original residue number in PDB)		Y304 L319 F327 E444 V503 F577 S578 W579 F580
Binding residue
(residue number reindexed from 1)		Y292 L307 F315 E432 V491 F565 S566 W567 F568
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=9.00,Kd<1nM
BindingDB: IC50=47nM
Enzymatic activity
Enzyme Commision number 2.1.1.320: type II protein arginine methyltransferase.
Gene Ontology
Molecular Function
GO:0002039 p53 binding
GO:0003714 transcription corepressor activity
GO:0005515 protein binding
GO:0008168 methyltransferase activity
GO:0008327 methyl-CpG binding
GO:0008469 histone arginine N-methyltransferase activity
GO:0016274 protein-arginine N-methyltransferase activity
GO:0035243 protein-arginine omega-N symmetric methyltransferase activity
GO:0042054 histone methyltransferase activity
GO:0042802 identical protein binding
GO:0043021 ribonucleoprotein complex binding
GO:0044020 histone H4R3 methyltransferase activity
GO:0044877 protein-containing complex binding
GO:0046982 protein heterodimerization activity
GO:0070888 E-box binding
GO:0140938 histone H3 methyltransferase activity
Biological Process
GO:0000387 spliceosomal snRNP assembly
GO:0006325 chromatin organization
GO:0006338 chromatin remodeling
GO:0006353 DNA-templated transcription termination
GO:0006355 regulation of DNA-templated transcription
GO:0006479 protein methylation
GO:0007088 regulation of mitotic nuclear division
GO:0010468 regulation of gene expression
GO:0018216 peptidyl-arginine methylation
GO:0032259 methylation
GO:0032922 circadian regulation of gene expression
GO:0035246 peptidyl-arginine N-methylation
GO:0042118 endothelial cell activation
GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation
GO:0045596 negative regulation of cell differentiation
GO:0045892 negative regulation of DNA-templated transcription
GO:0048026 positive regulation of mRNA splicing, via spliceosome
GO:0048511 rhythmic process
GO:0048714 positive regulation of oligodendrocyte differentiation
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0090161 Golgi ribbon formation
GO:0097421 liver regeneration
GO:1901796 regulation of signal transduction by p53 class mediator
GO:1904992 positive regulation of adenylate cyclase-inhibiting dopamine receptor signaling pathway
Cellular Component
GO:0000785 chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005737 cytoplasm
GO:0005794 Golgi apparatus
GO:0005829 cytosol
GO:0032991 protein-containing complex
GO:0034709 methylosome
GO:0035097 histone methyltransferase complex

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4x61, PDBe:4x61, PDBj:4x61
PDBsum4x61
PubMed25915199
UniProtO14744|ANM5_HUMAN Protein arginine N-methyltransferase 5 (Gene Name=PRMT5)

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