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Human histone demethylase KDM6B can catalyse sequential oxidations

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posted on 2018-06-07, 08:04 authored by Richard J. Hopkinson, Gareth W. Langley, Roman Belle, Louise J. Walport, Kate Dunne, MMartin Münzel, Eidarus Salah, Akane Kawamura, Timothy D. W. Claridge, Christopher J. Schofield
Jumonji domain‐containing demethylases (JmjC‐KDMs) catalyse demethylation of Nε ‐methylated lysines on histones and play important rolesin 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 Nε ‐alkylated lysine analogues, forming alcohol, aldehyde and carboxylic acid products.

Funding

We thank the Biotechnology and Biological Sciences Research Council (BB/J003018/1 and BB/L009846/1), Cancer Research UK (C8717/A18245), the Systems Approaches to Biomedical Science Industrial Doctoral Centre (supported by UCB and the Engineering and Physical Sciences Research Council, EP/G037280/1, G.W.L), the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007‐2013) under REA grant agreement no. 298603 (Marie Curie IEF Fellowship to M.M), and the Wellcome Trust (091857/7/10/7) for funding the work. R.J.H acknowledges a William R. Miller Junior Research Fellowship, St. Edmund Hall, Oxford, UK. K.D. acknowledges support from the BHF Centre of Research Excellence, Oxford (RE/08/004). We also acknowledge a Royal Society Dorothy Hodgkin Fellowship (A.K).

History

Citation

Chemical Communications, 2018, 54, pp. 7975-7978

Author affiliation

/Organisation/COLLEGE OF SCIENCE AND ENGINEERING/Department of Chemistry

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  • VoR (Version of Record)

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Chemical Communications

Publisher

Royal Society of Chemistry

issn

1359-7345

eissn

1364-548X

Acceptance date

2018-06-06

Copyright date

2018

Available date

2018-07-21

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https://pubs.rsc.org/en/content/articlehtml/2018/cc/c8cc04057e

Language

en

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