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The protein arginine deiminases: Structure, function, inhibition, and disease†
Article first published online: 22 NOV 2012
Copyright © 2012 Wiley Periodicals, Inc.
Special Issue: Chromatin Modifying Enzymes
Volume 99, Issue 2, pages 155–163, February 2013
How to Cite
Bicker, K. L. and Thompson, P. R. (2013), The protein arginine deiminases: Structure, function, inhibition, and disease. Biopolymers, 99: 155–163. doi: 10.1002/bip.22127
- Issue published online: 22 NOV 2012
- Article first published online: 22 NOV 2012
- Accepted manuscript online: 17 JUL 2012 04:32AM EST
- Manuscript Accepted: 6 JUL 2012
- Manuscript Revised: 24 JUN 2012
- Manuscript Received: 2 APR 2012
- post-translational modification
The post-translational modification of histones has significant effects on overall chromatin function. One such modification is citrullination, which is catalyzed by the protein arginine deiminases (PADs), a unique family of enzymes that catalyzes the hydrolysis of peptidyl-arginine to form peptidyl-citrulline on histones, fibrinogen, and other biologically relevant proteins. Overexpression and/or increased PAD activity is observed in several diseases, including rheumatoid arthritis, Alzheimer's disease, multiple sclerosis, lupus, Parkinson's disease, and cancer. This review discusses the important structural and mechanistic characteristics of the PADs, as well as recent investigations into the role of the PADs in increasing disease severity in RA and colitis and the importance of PAD activity in mediating neutrophil extracellular trap formation through chromatin decondensation. Lastly, efforts to develop PAD inhibitors with excellent potency, selectivity and in vivo efficacy are discussed, highlighting the most promising inhibitors. © 2012 Wiley Periodicals, Inc. Biopolymers 99: 155–163, 2013.