Journal
JOURNAL OF STRUCTURAL BIOLOGY
Volume 191, Issue 2, Pages 175-183Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jsb.2015.06.017
Keywords
Methyltransferase; PRMT6; Epigenetics; Protein structure; S-adenosyl-L-methionine
Funding
- Agence Nationale de la Recherche [ANR-08-PCVI-0037-01]
- Association pour la Recherche contre le Cancer (ARC) [A09/4/5005, SFI20121205902]
- Institut de Recherches Servier (Croissy-sur-Seine, France)
- Agence Nationale de la Recherche (ANR) [ANR-08-PCVI-0037] Funding Source: Agence Nationale de la Recherche (ANR)
Ask authors/readers for more resources
PRMT6 is a protein arginine methyltransferase involved in transcriptional regulation, human immunodeficiency virus pathogenesis, DNA base excision repair, and cell cycle progression. Like other PRMTs, PRMT6 is overexpressed in several cancer types and is therefore considered as a potential anti-cancer drug target. In the present study, we described six crystal structures of PRMT6 from Mus musculus, solved and refined at 1.34 angstrom for the highest resolution structure. The crystal structures revealed that the folding of the helix alpha X is required to stabilize a productive active site before methylation of the bound peptide can occur. In the absence of cofactor, metal cations can be found in the catalytic pocket at the expected position of the guanidinium moiety of the target arginine substrate. Using mass spectrometry under native conditions, we show that PRMT6 dimer binds two cofactor and a single H4 peptide molecules. Finally, we characterized a new site of in vitro automethylation of mouse PRMT6 at position 7. (C) 2015 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available