JMJD5 is a human arginyl C-3 hydroxylase
<p>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 essent...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Journal article |
| Published: |
Springer Nature
2018
|
| _version_ | 1797067097836093440 |
|---|---|
| author | Wilkins, S Islam, M Gannon, J Markolovic, S Hopkinson, R Ge, W Schofield, C Chowdhury, R |
| author_facet | Wilkins, S Islam, M Gannon, J Markolovic, S Hopkinson, R Ge, W Schofield, C Chowdhury, R |
| author_sort | Wilkins, S |
| collection | OXFORD |
| description | <p>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.</p> |
| first_indexed | 2024-03-06T21:51:27Z |
| format | Journal article |
| id | oxford-uuid:4b6981ff-7976-4647-a72b-bdd6419b5a13 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T21:51:27Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:4b6981ff-7976-4647-a72b-bdd6419b5a132022-03-26T15:43:26ZJMJD5 is a human arginyl C-3 hydroxylaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4b6981ff-7976-4647-a72b-bdd6419b5a13Symplectic Elements at OxfordSpringer Nature2018Wilkins, SIslam, MGannon, JMarkolovic, SHopkinson, RGe, WSchofield, CChowdhury, R<p>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.</p> |
| spellingShingle | Wilkins, S Islam, M Gannon, J Markolovic, S Hopkinson, R Ge, W Schofield, C Chowdhury, R JMJD5 is a human arginyl C-3 hydroxylase |
| title | JMJD5 is a human arginyl C-3 hydroxylase |
| title_full | JMJD5 is a human arginyl C-3 hydroxylase |
| title_fullStr | JMJD5 is a human arginyl C-3 hydroxylase |
| title_full_unstemmed | JMJD5 is a human arginyl C-3 hydroxylase |
| title_short | JMJD5 is a human arginyl C-3 hydroxylase |
| title_sort | jmjd5 is a human arginyl c 3 hydroxylase |
| work_keys_str_mv | AT wilkinss jmjd5isahumanarginylc3hydroxylase AT islamm jmjd5isahumanarginylc3hydroxylase AT gannonj jmjd5isahumanarginylc3hydroxylase AT markolovics jmjd5isahumanarginylc3hydroxylase AT hopkinsonr jmjd5isahumanarginylc3hydroxylase AT gew jmjd5isahumanarginylc3hydroxylase AT schofieldc jmjd5isahumanarginylc3hydroxylase AT chowdhuryr jmjd5isahumanarginylc3hydroxylase |