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Substrate Specificity of Human Protein Arginine Methyltransferase 7 (PRMT7): The Importance of Acidic Residues in the Double E Loop

Substrate Specificity of Human Protein Arginine Methyltransferase 7 (PRMT7): The Importance of Acidic Residues in the Double E Loop

You Feng, Andrea Hadjikyriacou, Steven G Clarke

J Biol Chem. 2014 Nov 21;289(47):32604-16.

PMID: 25294873

Abstract:

Protein arginine methyltransferase 7 (PRMT7) methylates arginine residues on various protein substrates and is involved in DNA transcription, RNA splicing, DNA repair, cell differentiation, and metastasis. The substrate sequences it recognizes in vivo and the enzymatic mechanism behind it, however, remain to be explored. Here we characterize methylation catalyzed by a bacterially expressed GST-tagged human PRMT7 fusion protein with a broad range of peptide and protein substrates. After confirming its type III activity generating only ω-N(G)-monomethylarginine and its distinct substrate specificity for RXR motifs surrounded by basic residues, we performed site-directed mutagenesis studies on this enzyme, revealing that two acidic residues within the double E loop, Asp-147 and Glu-149, modulate the substrate preference. Furthermore, altering a single acidic residue, Glu-478, on the C-terminal domain to glutamine nearly abolished the activity of the enzyme. Additionally, we demonstrate that PRMT7 has unusual temperature dependence and salt tolerance. These results provide a biochemical foundation to understanding the broad biological functions of PRMT7 in health and disease.

Chemicals Related in the Paper:

Catalog Number	Product Name	Price
IAR42411820	CAMK1δ, active, GST tagged human	Price
IAR42416117	PRMT7 human	Price
IAR42416204	p70S6Kb, active, GST tagged human	Price

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