5LGS

Crystal structure of mouse CARM1 in complex with ligand P2C3u

Summary for 5LGS

• Entry DOI: 10.2210/pdb5lgs/pdb
• Descriptor: Histone-arginine methyltransferase CARM1, Polyadenylate-binding protein 1, SULFATE ION, ... (9 entities in total)
• Functional Keywords: protein arginine methyltransferase, catalytic domain, chromatin regulator, mrna processing, mrna splicing, nucleus, s-adenosyl-l-methionine, transcription, transcription regulation, transferase
• Biological source: Mus musculus (Mouse); More
• Cellular location: Nucleus: Q9WVG6; Cytoplasm: P11940
• Total number of polymer chains: 8
• Total formula weight: 169124.22

Authors

Marechal, N.,Troffer-Charlier, N.,Cura, V.,Bonnefond, L.,Cavarelli, J. (deposition date: 2016-07-08, release date: 2017-03-22, Last modification date: 2024-10-16)

Primary citation

van Haren, M.J.,Marechal, N.,Troffer-Charlier, N.,Cianciulli, A.,Sbardella, G.,Cavarelli, J.,Martin, N.I.
Transition state mimics are valuable mechanistic probes for structural studies with the arginine methyltransferase CARM1.
Proc. Natl. Acad. Sci. U.S.A., 114:3625-3630, 2017

PubMed Abstract: Coactivator associated arginine methyltransferase 1 (CARM1) is a member of the protein arginine methyltransferase (PRMT) family and methylates a range of proteins in eukaryotic cells. Overexpression of CARM1 is implicated in a number of cancers, and it is therefore seen as a potential therapeutic target. Peptide sequences derived from the well-defined CARM1 substrate poly(A)-binding protein 1 (PABP1) were covalently linked to an adenosine moiety as in the AdoMet cofactor to generate transition state mimics. These constructs were found to be potent CARM1 inhibitors and also formed stable complexes with the enzyme. High-resolution crystal structures of CARM1 in complex with these compounds confirm a mode of binding that is indeed reflective of the transition state at the CARM1 active site. Given the transient nature of PRMT-substrate complexes, such transition state mimics represent valuable chemical tools for structural studies aimed at deciphering the regulation of arginine methylation mediated by the family of arginine methyltransferases.

PubMed: 28330993
DOI: 10.1073/pnas.1618401114

Experimental method

X-RAY DIFFRACTION (2.1 Å)