Journal article icon

Journal article

JMJD5 is a human arginyl C-3 hydroxylase

Abstract:

Oxygenase catalysed post-translational modifications of basic protein residues including lysyl hydroxylations and Nε-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 Nε-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.

Publication status:
Published
Peer review status:
Peer reviewed

Actions

Access Document

Files:
Publisher copy:
10.1038/s41467-018-03410-w

Authors

More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry; Organic Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry; Organic Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry; Organic Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry; Organic Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry; Organic Chemistry
Role:
Author



Publisher:
Springer Nature
Journal:
Nature Communications More from this journal
Volume:
9
Article number:
1180
Publication date:
2018-03-21
Acceptance date:
2018-03-05
DOI:
EISSN:
2041-1723
ISSN:
2041-1723


Pubs id:
pubs:830024
UUID:
uuid:4b6981ff-7976-4647-a72b-bdd6419b5a13
Local pid:
pubs:830024
Deposit date:
2018-03-19
ARK identifier:

Terms of use


Views and Downloads






If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP