JMJD5 is a human arginyl C-3 hydroxylase.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29563586.
- Also identified by DOI 10.1038/s41467-018-03410-w and PMC identifier 5862942.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Oxygenase-catalysed post-translational modifications of basic protein residues, including lysyl hydroxylations and N<sup>ε</sup>-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 N<sup>ε</sup>-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.
Medical subject headings
- Arginine
- Carrier Proteins
- Histone Demethylases
- Membrane Proteins
- Ribosomal Protein S6