Peptidyl Arginine Deiminase Type 4

Peptidyl Arginine Deiminases (PADs) perform post-translational deiminations of proteins. PADs are calcium-dependent enzymes that catalyze the conversion of L-arginine residues to L-citrulline. The catalyzed reaction is as follows:

²⁺ Ca Protein--[L-arginine] + H2O ––––> Protein--[L-citrulline]

There are five mammalian PADs sub-types, which differ in substrate specificity and tissue distribution. PAD enzymes are highly homologous, with 50–60% sequence similarity.¹ PADs play important roles in gene regulation by citrullination of arginine residues on histones H3, H2A, and H4. Overexpression of PADs has been found in conditions such as rheumatoid arthritis, Alzheimer′s disease, multiple sclerosis, lupus,Parkinson′s disease, and cancer.^2,3

PAD4 is widely expressed in the immune system with expression pathology in various tumor and cancer cell lines.⁵ In cells, PAD4 can be found in the cytoplasm and nucleus. PAD4 activity has been correlated to the development and progress of Rheumatoid Arthritis (RA).^2,5 A study in mice has indicated a mechanism for the development of RA by anticitrullin autoimmunity.⁶

This recombinant human PAD4 is expressed in Escherichia coli as a fusion protein. The fusion partner is removed by HRV3C protease digestion, followed by chromatographic purification.

One unit will produce 1 μmole of N-a-benzoylcitrulline ethyl ester from BAEE per hour at 37 °C at pH 7.7.

Calcium is required for peptidylarginine deiminase activity in vitro.

Supplied as an aqueous solution in 10 mM Tris (pH 7.5), 500 mM NaCl, 1 mM EDTA, and 1 mM DTT.