Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-03

AUTHORS

Yanqi Chang, Xing Zhang, John R Horton, Anup K Upadhyay, Astrid Spannhoff, Jin Liu, James P Snyder, Mark T Bedford, Xiaodong Cheng

ABSTRACT

Histone lysine methylation is an important epigenetic mark that regulates gene expression and chromatin organization. G9a and G9a-like protein (GLP) are euchromatin-associated methyltransferases that repress transcription by methylating histone H3 Lys9. BIX-01294 was originally identified as a G9a inhibitor during a chemical library screen of small molecules and has previously been used in the generation of induced pluripotent stem cells. Here we present the crystal structure of the catalytic SET domain of GLP in complex with BIX-01294 and S-adenosyl-L-homocysteine. The inhibitor is bound in the substrate peptide groove at the location where the histone H3 residues N-terminal to the target lysine lie in the previously solved structure of the complex with histone peptide. The inhibitor resembles the bound conformation of histone H3 Lys4 to Arg8, and is positioned in place by residues specific for G9a and GLP through specific interactions. More... »

PAGES

312-317

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nsmb.1560

DOI

http://dx.doi.org/10.1038/nsmb.1560

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1030525601

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19219047


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/nsmb.1560'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/nsmb.1560'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/nsmb.1560'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/nsmb.1560'


 

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