Structural highlights
Function
[KDM8_HUMAN] Histone demethylase required for G2/M phase cell cycle progression. Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator. Regulates expression of CCNA1 (cyclin-A1), leading to regulate cancer cell proliferation.
Publication Abstract from PubMed
Oxygenase-catalysed post-translational modifications of basic protein residues, including lysyl hydroxylations and N(epsilon)-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(epsilon)-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.
JMJD5 is a human arginyl C-3 hydroxylase.,Wilkins SE, Islam S, Gannon JM, Markolovic S, Hopkinson RJ, Ge W, Schofield CJ, Chowdhury R Nat Commun. 2018 Mar 21;9(1):1180. doi: 10.1038/s41467-018-03410-w. PMID:29563586[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wilkins SE, Islam S, Gannon JM, Markolovic S, Hopkinson RJ, Ge W, Schofield CJ, Chowdhury R. JMJD5 is a human arginyl C-3 hydroxylase. Nat Commun. 2018 Mar 21;9(1):1180. doi: 10.1038/s41467-018-03410-w. PMID:29563586 doi:http://dx.doi.org/10.1038/s41467-018-03410-w
