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JMJD5 is a human arginyl C-3 hydroxylase.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Wilkins, Sarah E 
Islam, Md Saiful 
Gannon, Joan M 
Markolovic, Suzana 
Hopkinson, Richard J  ORCID logo  https://orcid.org/0000-0001-7610-8163

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.

Description

Keywords

Arginine, Carrier Proteins, Catalytic Domain, Cloning, Molecular, Crystallography, X-Ray, Escherichia coli, Gene Expression, Genetic Vectors, Histone Demethylases, Humans, Hydroxylation, Kinetics, Lysine, Membrane Proteins, Models, Molecular, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Folding, Protein Interaction Domains and Motifs, Recombinant Proteins, Ribosomal Protein S6, Stereoisomerism, Substrate Specificity, Thermodynamics

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

9

Publisher

Springer Science and Business Media LLC