Structure of PDB 4y30 Chain B Binding Site BS02

Receptor Information

>4y30 Chain B (length=351) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]

DGAEREAALERPRRTKRERDQLYYECYSDVSVHEEMIADRVRTDAYRLGI
LRNWAALRGKTVLDVGAGTGILSIFCAQAGARRVYAVEASAIWQQAREVV
RFNGLEDRVHVLPGPVETVELPEQVDAIVSEWMGYGLLHESMLSSVLHAR
TKWLKEGGLLLPASAELFIAPISDQMLEWRLGFWSQVKQHYGVDMSCLEG
FATRCLMGHSEIVVQGLSGEDVLARPQRFAQLELSRAGLEQELQAGVGGR
FRCSCYGSAPMHGFAIWFQVTFPGGESEKPLVLSTSPFHPATHWKQALLY
LNEPVQVEQDTDVSGEITLLPSRDNPRRLRVLLRYKVGDQEEKTKDFAME
D

Ligand information

Ligand ID

49L

InChI

InChI=1S/C25H38N4O3/c1-26-10-11-29(2)18-21-17-27-28-25(21)20-3-5-22(6-4-20)32-24-15-23(16-24)31-14-9-19-7-12-30-13-8-19/h3-6,17,19,23-24,26H,7-16,18H2,1-2H3,(H,27,28)/t23-,24-

InChIKey

QMDKVNSQXPVCRD-RQNOJGIXSA-N

SMILES

Software	SMILES
CACTVS 3.385	CNCCN(C)Cc1c[nH]nc1c2ccc(O[CH]3C[CH](C3)OCCC4CCOCC4)cc2
CACTVS 3.385	CNCCN(C)Cc1c[nH]nc1c2ccc(O[C@H]3C[C@@H](C3)OCCC4CCOCC4)cc2
ACDLabs 12.01	O(CCC1CCOCC1)C4CC(Oc3ccc(c2nncc2CN(CCNC)C)cc3)C4
OpenEye OEToolkits 1.9.2	CNCCN(C)Cc1c[nH]nc1c2ccc(cc2)OC3CC(C3)OCCC4CCOCC4

Formula

C25 H38 N4 O3

Name

N,N'-dimethyl-N-({3-[4-({trans-3-[2-(tetrahydro-2H-pyran-4-yl)ethoxy]cyclobutyl}oxy)phenyl]-1H-pyrazol-4-yl}methyl)ethane-1,2-diamine

PDB chain

4y30 Chain B Residue 402 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]

Receptor-Ligand Complex Structure

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Structure summary

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PDB	4y30 Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound.
Resolution	2.1 Å
Binding residue (original residue number in PDB)	R43 L46 Y51 E59 M60 E155 W156 M157 E164 H317 N349
Binding residue (residue number reindexed from 1)	R19 L22 Y27 E35 M36 E131 W132 M133 E140 H293 N325
Annotation score	1
Binding affinity	MOAD: ic50=10nM BindingDB: IC50=10.0nM

Enzymatic activity

Catalytic site (original residue number in PDB)	D63 E155 E164 H317
Catalytic site (residue number reindexed from 1)	D39 E131 E140 H293
Enzyme Commision number	2.1.1.319: type I protein arginine methyltransferase.

Gene Ontology

	Molecular Function
GO:0003682	chromatin binding
GO:0005515	protein binding
GO:0008168	methyltransferase activity
GO:0008469	histone arginine N-methyltransferase activity
GO:0016274	protein-arginine N-methyltransferase activity
GO:0035241	protein-arginine omega-N monomethyltransferase activity
GO:0035242	protein-arginine omega-N asymmetric methyltransferase activity
GO:0042054	histone methyltransferase activity
GO:0042393	histone binding
GO:0044020	histone H4R3 methyltransferase activity
GO:0070611	histone H3R2 methyltransferase activity
GO:0070612	histone H2AR3 methyltransferase activity
GO:0140938	histone H3 methyltransferase activity

	Biological Process
GO:0000122	negative regulation of transcription by RNA polymerase II
GO:0006281	DNA repair
GO:0006284	base-excision repair
GO:0006325	chromatin organization
GO:0006338	chromatin remodeling
GO:0010821	regulation of mitochondrion organization
GO:0018216	peptidyl-arginine methylation
GO:0032259	methylation
GO:0036211	protein modification process
GO:0045652	regulation of megakaryocyte differentiation
GO:0045892	negative regulation of DNA-templated transcription
GO:0090398	cellular senescence
GO:1901796	regulation of signal transduction by p53 class mediator
GO:2000059	negative regulation of ubiquitin-dependent protein catabolic process

	Cellular Component
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005730	nucleolus

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Molecular Function

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Biological Process

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Cellular Component

External links

PDB	RCSB:4y30, PDBe:4y30, PDBj:4y30
PDBsum	4y30
PubMed	26101569
UniProt	Q96LA8\|ANM6_HUMAN Protein arginine N-methyltransferase 6 (Gene Name=PRMT6)

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