Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation.

ABSTRACT: Protein citrullination is just one of more than 200 known PTMs. This modification, catalyzed by the protein arginine deiminases (PADs 1-4 and PAD6 in humans), converts the positively charged guanidinium group of an arginine residue into a neutral ureido-group. Given the strong links between dysregulated PAD activity and human disease, we initiated a program to develop PAD inhibitors as potential therapeutics for these and other diseases in which the PADs are thought to play a role. Streptonigrin which possesses both anti-tumor and anti-bacterial activity was later identified as a highly potent PAD4 inhibitor. In an effort to understand why streptonigrin is such a potent and selective PAD4 inhibitor, we explored its structure-activity relationships by examining the inhibitory effects of sev

SUBMITTER: Dreyton CJ 

PROVIDER: S-EPMC3954981 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature