4C05

Crystal structure of M. musculus protein arginine methyltransferase PRMT6 with SAH

Summary for 4C05

• Entry DOI: 10.2210/pdb4c05/pdb
• Related: 4C03 4C04 4C06 4C07 4C08
• Descriptor: PROTEIN ARGININE N-METHYLTRANSFERASE 6, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: transferase
• Biological source: MUS MUSCULUS (HOUSE MOUSE)
• Cellular location: Nucleus : Q6NZB1
• Total number of polymer chains: 1
• Total formula weight: 42706.20

Authors

Bonnefond, L.,Cura, V.,Troffer-Charlier, N.,Mailliot, J.,Wurtz, J.M.,Cavarelli, J. (deposition date: 2013-07-31, release date: 2014-07-30, Last modification date: 2023-12-20)

Primary citation

Bonnefond, L.,Stojko, J.,Mailliot, J.,Troffer-Charlier, N.,Cura, V.,Wurtz, J.M.,Cianferani, S.,Cavarelli, J.
Functional Insights from High Resolution Structures of Mouse Protein Arginine Methyltransferase 6.
J.Struct.Biol., 191:175-, 2015

PubMed Abstract: 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 Å for the highest resolution structure. The crystal structures revealed that the folding of the helix αX 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.

PubMed: 26094878
DOI: 10.1016/J.JSB.2015.06.017

Experimental method

X-RAY DIFFRACTION (2.195 Å)