Title

Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation.

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Date

3-1-2015

Document Type

Article

Medical Subject Headings

Animals; Binding, Competitive; Calcium; Citrulline; Enzyme Inhibitors; HEK293 Cells; Histones; Humans; Hydrolases; In Vitro Techniques; Mice; Models, Molecular; Neutrophils; Small Molecule Libraries; Substrate Specificity

Disciplines

Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics

Abstract

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.

Rights and Permissions

Citation: Nat Chem Biol. 2015 Mar;11(3):189-91. doi: 10.1038/nchembio.1735. Link to article on publisher's site

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed