3UA3

Crystal Structure of Protein Arginine Methyltransferase PRMT5 in complex with SAH

Summary for 3UA3

• Entry DOI: 10.2210/pdb3ua3/pdb
• Related: 3UA4
• Descriptor: Protein arginine N-methyltransferase 5, S-ADENOSYL-L-HOMOCYSTEINE (3 entities in total)
• Functional Keywords: tim-barrel, rossmann fold, beta-barrel, symmetric arginine dimethylase, sam binding, symmetric dimethylation, nucleus, transferase
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 2
• Total formula weight: 171858.74

Authors

Sun, L.,Wang, M.,Lv, Z.,Yang, N.,Liu, Y.,Bao, S.,Gong, W.,Xu, R.M. (deposition date: 2011-10-20, release date: 2011-12-14, Last modification date: 2011-12-28)

Primary citation

Sun, L.,Wang, M.,Lv, Z.,Yang, N.,Liu, Y.,Bao, S.,Gong, W.,Xu, R.M.
Structural insights into protein arginine symmetric dimethylation by PRMT5
Proc.Natl.Acad.Sci.USA, 108:20538-20543, 2011

PubMed Abstract: Symmetric and asymmetric dimethylation of arginine are isomeric protein posttranslational modifications with distinct biological effects, evidenced by the methylation of arginine 3 of histone H4 (H4R3): symmetric dimethylation of H4R3 leads to repression of gene expression, while asymmetric dimethylation of H4R3 is associated with gene activation. The enzymes catalyzing these modifications share identifiable sequence similarities, but the relationship between their catalytic mechanisms is unknown. Here we analyzed the structure of a prototypic symmetric arginine dimethylase, PRMT5, and discovered that a conserved phenylalanine in the active site is critical for specifying symmetric addition of methyl groups. Changing it to a methionine significantly elevates the overall methylase activity, but also converts PRMT5 to an enzyme that catalyzes both symmetric and asymmetric dimethylation of arginine. Our results demonstrate a common catalytic mechanism intrinsic to both symmetric and asymmetric arginine dimethylases, and show that steric constrains in the active sites play an essential role in determining the product specificity of arginine methylases. This discovery also implies a potentially regulatable outcome of arginine dimethylation that may provide versatile control of eukaryotic gene expression.

PubMed: 22143770
DOI: 10.1073/pnas.1106946108

Experimental method

X-RAY DIFFRACTION (3 Å)