Human histone demethylase KDM6B can catalyse sequential oxidations

Richard J. Hopkinson; Gareth W. Langley; Roman Belle; Louise J. Walport; Kate Dunne; Martin Münzel; Eidarus Salah; Akane Kawamura; Timothy D. W. Claridge; Christopher J. Schofield

doi:10.1039/C8CC04057E

Human histone demethylase KDM6B can catalyse sequential oxidations†

Richard J. Hopkinson,

*^ab Gareth W. Langley,

^a Roman Belle,

^a Louise J. Walport,

^a Kate Dunne,^ac Martin Münzel,^a Eidarus Salah,^a Akane Kawamura,

^ac Timothy D. W. Claridge

^a and Christopher J. Schofield

*^a

Author affiliations

* Corresponding authors

^a Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, UK
E-mail: christopher.schofield@chem.ox.ac.uk

^b Leicester Institute of Structural and Chemical Biology and Department of Chemistry, University of Leicester, Lancaster Road, Leicester, UK
E-mail: richard.hopkinson@leicester.ac.uk

^c Radcliffe Department of Medicine, Division of Cardiovascular Medicine, BHF Centre of Research Excellence, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, UK

Abstract

Jumonji domain-containing demethylases (JmjC-KDMs) catalyse demethylation of N^ε-methylated lysines on histones and play important roles in gene regulation. We report selectivity studies on KDM6B (JMJD3), a disease-relevant JmjC-KDM, using synthetic lysine analogues. The results unexpectedly reveal that KDM6B accepts multiple N^ε-alkylated lysine analogues, forming alcohol, aldehyde and carboxylic acid products.

Chemical Communications

Human histone demethylase KDM6B can catalyse sequential oxidations†

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Human histone demethylase KDM6B can catalyse sequential oxidations

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