Discovery and characterisation of the automethylation properties of PRDM9
| Autor: | Xiaoying Koh-Stenta, Perlyn Zekui Kwek, Sin Yin Chew, Jeffrey Hill, Anders Poulsen, Rong Li, Liling Wu, Ernesto Guccione, Joma Joy, John Liang Kuan Wee, Jianhe Peng |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation alpha-Helical Proline Lysine Gene Expression medicine.disease_cause Ligands Biochemistry Methylation 03 medical and health sciences Mice 0302 clinical medicine Protein Domains Catalytic Domain medicine Escherichia coli Animals Amino Acid Sequence Cysteine Cloning Molecular Enhancer Molecular Biology PRDM9 Variegation Mutation biology Rational design Cell Biology Histone-Lysine N-Methyltransferase Recombinant Proteins Cell biology Kinetics 030104 developmental biology Histone Amino Acid Substitution 030220 oncology & carcinogenesis Histone methyltransferase biology.protein Protein Conformation beta-Strand Protein Processing Post-Translational Protein Binding |
| Zdroj: | The Biochemical journal. 474(6) |
| ISSN: | 1470-8728 |
| Popis: | We have previously characterised the histone lysine methyltransferase properties of PRDM9, a member of the PRDM family of putative transcriptional regulators. PRDM9 displays broad substrate recognition and methylates a range of histone substrates, including octamers, core histone proteins, and peptides. In the present study, we show that PRDM9 performs intramolecular automethylation on multiple lysine residues localised to a lysine-rich region on the post-SET (suppressor of variegation 3–9, enhancer of zeste and trithorax) domain. PRDM9 automethylation is abolished by a single active-site mutation, C321P, also known to disrupt interactions with S-adenosylmethionine. We have taken an initial step towards tool compound generation through rational design of a substrate-mimic, peptidic inhibitor of PRDM9 automethylation. The discovery of automethylation in PRDM9 adds a new dimension to our understanding of PRDM9 enzymology. |
| Databáze: | OpenAIRE |
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