Theoretical study of the mechanism of protein arginine deiminase 4 (PAD4) inhibition by F-amidine

In the PAD4-F-amidine reactant complex, the active site Cys645 exists as a thiolate and His471 is protonated. The inhibition reaction proceeds through a three-membered sulfonium ring transition state, His471 acts as a proton donor and facilitates the inhibition.