Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.
Department of Biochemistry and Molecular Pharmacology
Animals; Binding, Competitive; Calcium; Citrulline; Enzyme Inhibitors; HEK293 Cells; Histones; Humans; Hydrolases; In Vitro Techniques; Mice; Models, Molecular; Neutrophils; Small Molecule Libraries; Substrate Specificity
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation for, to our knowledge, the first time. The therapeutic potential of PAD4 inhibitors can now be explored.
DOI of Published Version
Nat Chem Biol. 2015 Mar;11(3):189-91. doi: 10.1038/nchembio.1735. Link to article on publisher's site
Nature chemical biology
Lewis HD, Thompson PR. (2015). Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.. Thompson Lab Publications. https://doi.org/10.1038/nchembio.1735. Retrieved from https://escholarship.umassmed.edu/thompson/4