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JMJD5 is a human arginyl C-3 hydroxylase

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posted on 2018-04-09, 13:46 authored by Sarah E. Wilkins, Md. Saiful Islam, Joan M. Gannon, Suzana Markolovic, Richard J. Hopkinson, Wei Ge, Christopher J. Schofield, Rasheduzzaman Chowdhury
Oxygenase-catalysed post-translational modifications of basic protein residues, including lysyl hydroxylations and Nε-methyl lysyl demethylations, have important cellular roles. Jumonji-C (JmjC) domain-containing protein 5 (JMJD5), which genetic studies reveal is essential in animal development, is reported as a histone Nε-methyl lysine demethylase (KDM). Here we report how extensive screening with peptides based on JMJD5 interacting proteins led to the finding that JMJD5 catalyses stereoselective C-3 hydroxylation of arginine residues in sequences from human regulator of chromosome condensation domain-containing protein 1 (RCCD1) and ribosomal protein S6 (RPS6). High-resolution crystallographic analyses reveal overall fold, active site and substrate binding/product release features supporting the assignment of JMJD5 as an arginine hydroxylase rather than a KDM. The results will be useful in the development of selective oxygenase inhibitors for the treatment of cancer and genetic diseases.

History

Citation

Nature Communications, 2018, 9, 1180

Author affiliation

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

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  • VoR (Version of Record)

Published in

Nature Communications

Publisher

Nature Publishing Group

issn

2041-1723

Acceptance date

2018-02-12

Copyright date

2018

Available date

2018-04-09

Publisher version

https://www.nature.com/articles/s41467-018-03410-w

Notes

Publisher Correction: 23 April 2018 : The originally published version of this Article contained an error in the spelling of the author Md. Saiful Islam, which was incorrectly given as Saiful Islam. This has now been corrected in both the PDF and HTML versions of the Article.

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en

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