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JMJD5 is a human arginyl C-3 hydroxylase
DOI:
10.1038/s41467-018-03410-w
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

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
Diamond Keywords: Enzymes
Subject Areas:
Biology and Bio-materials,
Medicine
Instruments:
I03-Macromolecular Crystallography
Added On:
22/03/2018 08:58
Documents:
s41467-018-03410-w.pdf
Discipline Tags:
Non-Communicable Diseases
Health & Wellbeing
Cancer
Structural biology
Drug Discovery
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)