Arginine Deiminase Uses an Active-Site Cysteine in Nucleophilic Catalysis of L-Arginine Hydrolysis

摘要

Arginine deiminase (EC 3.5.3.6) catalyzes the hydrolysis of L-arginine to citrulline and ammonium ion; the first step of the L-arginine degradation pathway used by specialized microorganisms as an essential pathway for energy production1 (Scheme 1). The deiminase has attracted much attention because it can be used to reduce nitric oxide levels2 and therefore serve as a cancer chemotheraputic agent targeting angiogenesis and tumor growth.3 With the recent discovery of the arginine degradation pathway in microbial pathogens, arginine deiminase has emerged as a novel drug target. It is within this context that investigations of the structure4 and the mechanism of catalysis of arginine deiminase from Pseudomonas aeruginosa were initiated in our laboratories.