6f4p
Human JMJD5 in complex with MN, NOG and RPS6 (129-144) (complex-1)Human JMJD5 in complex with MN, NOG and RPS6 (129-144) (complex-1)
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. [RS6_HUMAN] May play an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA. Publication Abstract from PubMedOxygenase-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
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OCA- 50S ribosomal protein L16 3-hydroxylase
- Chowdhury, R
- Islam, M S
- Schofield, C J
- 2-oxoglutarate
- 40s ribosomal protein s6
- Arginine hydroxylation
- Arginyl c-3 hydroxylase
- Beta-hydroxylation
- Cancer
- Cell structure
- Cytoplasm
- Development
- Dioxygenase
- Dna-binding
- Dsbh
- Epigenetic regulation
- Facial triad
- Hydroxylation
- Hypoxia
- Iron
- Jmjc
- Jmjc demethylase
- Jmjc domain
- Jmjc domain-containing protein 5
- Jmjc hydroxylase
- Jmjd5
- Kdm
- Kdm8
- Lysine-specific demethylase 8
- Metal-binding
- Non-heme
- Oxidoreductase
- Oxygenase
- Phosphorylation
- Polymorphism
- Post-translational modification
- Ptm
- Rcc1 domain-containing protein 1
- Rccd1
- Regulator of chromosome condensation
- Ribosome biogenesis
- Rps6
- Signaling
- Transcription
- Transcription activator/inhibitor
- Translation