PDBsum entry 6f4m

Oxidoreductase

PDB id: 6f4m

Contents

Protein chain

235 a.a.

Waters ×207

PDB id:

6f4m

Name:

Oxidoreductase

Title:

Human jmjd5 in its apo form.

Structure:

Jmjc domain-containing protein 5. Chain: a. Synonym: lysine-specific demethylase 8, jumonji domain-containing protein 5. Engineered: yes. Other_details: catalytic domain (residues 183-416)

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: kdm8, jmjd5. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.71Å R-factor: 0.171 R-free: 0.187

Authors:

R.Chowdhury,M.S.Islam,C.J.Schofield

Key ref:

S.E.Wilkins et al. (2018). JMJD5 is a human arginyl C-3 hydroxylase. Nat Commun, 9, 1180. PubMed id: 29563586

Date:

29-Nov-17 Release date: 04-Apr-18

Protein chain

Q8N371  (KDM8_HUMAN) -  Bifunctional peptidase and arginyl-hydroxylase JMJD5 from Homo sapiens

Seq: 416 a.a.

Struc: 235 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.1.14.11.73 - [protein]-arginine 3-hydroxylase.
• Reaction: L-arginyl-[protein] + 2-oxoglutarate + O2 = (3R)-3-hydroxy-L-arginyl- [protein] + succinate + CO2
• Enzyme class 2: E.C.3.4.-.-

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Nat Commun 9:1180 (2018)

PubMed id: 29563586

JMJD5 is a human arginyl C-3 hydroxylase.

S.E.Wilkins, S.Islam, J.M.Gannon, S.Markolovic, R.J.Hopkinson, W.Ge, C.J.Schofield, R.Chowdhury.

ABSTRACT

Oxygenase-catalysed post-translational modifications of basic protein residues, including lysyl hydroxylations and N^ε-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^ε-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.