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Development of the Protein Arginine Deiminase (PAD) Inhibitors

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Protein Deimination in Human Health and Disease

Abstract

The protein arginine deiminases (PADs) catalyze the hydrolysis of positively charged arginine residues to generate neutral citrulline. This reaction is a calciumdependent process wherein calcium binding triggers a conformational change that results in a >10,000-fold increase in activity (Liu et al. 2011; Kearney et al. 2005). There are five known PAD isozymes (PAD1–PAD4 and PAD6), of which only PAD1–PAD4 are catalytically active (Raijmakers et al. 2007). Dysregulated PAD activity has been associated with a variety of autoimmune diseases as well as cancers, with potentially distinct roles for the individual isozymes. Given the abundant evidence linking aberrant PAD activity to human disease, there is a pressing need to develop potent and isozyme-specific inhibitors for use as therapeutics and/or probes to decipher the full complement of processes regulated by these enzymes. Herein, we discuss the latest developments in this area.

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Authors and Affiliations

  1. University of Massachusetts Medical School, LRB 826, 364 Plantation Street, Worcester, MA, 01605, USA

    Aaron Muth & Paul R. Thompson

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  1. Aaron Muth
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  2. Paul R. Thompson
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Correspondence to Paul R. Thompson .

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Editors and Affiliations

  1. Department of Neurology, University of Alabama at Birmingham and The Birmingham Veterans Administration Medical Center, Birmingham, Alabama, USA

    Anthony P. Nicholas

  2. Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA

    Sanjoy K. Bhattacharya

  3. Department of Biochemistry and Molecular Pharmacology, UMASS Medical School, Worcester, Massachusetts, USA

    Paul R. Thompson

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Muth, A., Thompson, P.R. (2017). Development of the Protein Arginine Deiminase (PAD) Inhibitors. In: Nicholas, A., Bhattacharya, S., Thompson, P. (eds) Protein Deimination in Human Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-58244-3_23

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