title: Protein arginine N-methyltransferase substrate preferences for different nη-substituted arginyl peptides.
abstract: Protein arginine N-methyltransferases (PRMTs) catalyze methyl-group transfer from S-adenosyl-L-methionine onto arginine residues in proteins. In this study, modifications were introduced at the guanidine moiety of a peptidyl arginine residue to investigate how changes to the PRMT substrate can modulate enzyme activity. We found that peptides bearing Nη-hydroxy or Nη-amino substituted arginine showed higher apparent kcat values than for the monomethylated substrate when using PRMT1, whereas this catalytic preference was not observed for PRMT4 and PRMT6. Methylation by compromised PRMT1 variants E153Q and D51N further supports the finding that the N-hydroxy substitution facilitates methyl transfer by tuning the reactivity of the guanidine moiety. In contrast, Nη-nitro and Nη-canavanine substituted substrates inhibit PRMT activity. These findings demonstrate that methylation of these PRMT substrates is dependent on the nature of the modification at the guanidine moiety.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, 2405 Wesbrook Mall, Vancouver, British Columbia V6T 1Z3 (Canada).
authors.forename: Dylan
authors.initials: D
authors.lastname: Thomas
authors.forename: Timo
authors.initials: T
authors.lastname: Koopmans
authors.forename: Ted M
authors.initials: TM
authors.lastname: Lakowski
authors.forename: Helmi
authors.initials: H
authors.lastname: Kreinin
authors.forename: Mynol I
authors.initials: MI
authors.lastname: Vhuiyan
authors.forename: Shona A
authors.initials: SA
authors.lastname: Sedlock
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bui
authors.forename: Nathaniel I
authors.initials: NI
authors.lastname: Martin
authors.forename: Adam
authors.initials: A
authors.lastname: Frankel
mesh_terms: D001120:Arginine / Q000378:metabolism*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D010455:Peptides; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases
keywords: arginine analogues; enzymes; methylation; peptides; protein arginine N-methyltransferases