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JMJD5 is a human arginyl C-3 hydroxylase

DOI: 10.1038/s41467-018-03410-w DOI Help

Authors: Sarah E. Wilkins (University of Oxford) , Saiful Islam (University of Oxford) , Joan M. Gannon (University of Oxford) , Suzana Markolovic (University of Oxford) , Richard J. Hopkinson (University of Oxford) , Wei Ge (University of Oxford) , Christopher J. Schofield (University of Oxford) , Rasheduzzaman Chowdhury (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: March 2018

Open Access Open Access

Abstract: 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.

Journal Keywords: Enzyme mechanisms; High-throughput screening; Nanocrystallography; Post-translational modifications; Proteomics

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I03-Macromolecular Crystallography

Documents:
s41467-018-03410-w.pdf

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