6F4M

Human JMJD5 in its apo form.

Summary for 6F4M

• Entry DOI: 10.2210/pdb6f4m/pdb
• Related: 6F4N 6F4O 6F4P 6F4Q 6F4R 6F4S 6F4T
• Descriptor: JmjC domain-containing protein 5 (2 entities in total)
• Functional Keywords: oxidoreductase, non-heme, iron, 2-oxoglutarate, dioxygenase, jmjc, jmjc domain, lysine-specific demethylase 8, jmjc domain-containing protein 5, arginyl c-3 hydroxylase, jmjd5, kdm8, oxygenase, hypoxia, dna-binding, metal-binding, translation, dsbh, facial triad, cytoplasm, jmjc hydroxylase, jmjc demethylase, kdms, post-translational modifications, ptm, beta-hydroxylation, hydroxylation, arginine hydroxylation, rcc1 domain-containing protein 1, rccd1, regulator of chromosome condensation, 40s ribosomal protein s6, rps6, ribosome biogenesis, transcription, epigenetic regulation, signaling, development, cell structure, transcription activator/inhibitor, phosphorylation, cancer, polymorphism
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q8N371
• Total number of polymer chains: 1
• Total formula weight: 27133.61

Authors

Chowdhury, R.,Islam, M.S.,Schofield, C.J. (deposition date: 2017-11-29, release date: 2018-04-04, Last modification date: 2024-01-17)

Primary citation

Wilkins, S.E.,Islam, S.,Gannon, J.M.,Markolovic, S.,Hopkinson, R.J.,Ge, W.,Schofield, C.J.,Chowdhury, R.
JMJD5 is a human arginyl C-3 hydroxylase.
Nat Commun, 9:1180-1180, 2018

PubMed Abstract: Oxygenase-catalysed post-translational modifications of basic protein residues, including lysyl hydroxylations and N-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-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.

PubMed: 29563586
DOI: 10.1038/s41467-018-03410-w

Experimental method

X-RAY DIFFRACTION (1.705 Å)