Methylation of the guanidino group of arginine residues prevents citrullination by peptidylarginine deiminase IV.
Peptidylarginine deiminase IV (PAD IV) catalyzes the citrullination of Arg residues of proteins, such as histones. Suzuki et al. recently reported that haplotypes of the PAD IV gene are associated with susceptibility to rheumatoid arthritis. To investigate the mechanism of substrate specificity and inhibitors of PAD IV, a series of the Arg derivatives were synthesized and their reactivity to PAD IV examined. The results suggest that both imino and carboxyl groups are important in the molecular recognition of PAD IV and that methylation of the guanidino group prevents citrullination. In addition, the findings herein show that Bz-N(G)-monomethyl-Arg and Bz-N(G),N(G)-dimethyl-Arg specifically inhibit citrullination.
Hidaka
Yuji
Y
Department of Life Science, School of Science and Engineering, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577-8502, Japan. yuji@life.kindai.ac.jp
Hagiwara
Teruki
T
Yamada
Michiyuki
M
D001120:Arginine / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D002956:Citrulline / Q000378:metabolism*; D019791:Guanidine / Q000737:chemistry / Q000378:metabolism*; D006867:Hydrolases / Q000378:metabolism*; D008745:Methylation; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
D002956:Citrulline; D001120:Arginine; D006867:Hydrolases; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D019791:Guanidine