The Active Site of Nitrile Hydratase: An Assembly of Unusual Coordination Features by Nature

Abstract

Abstract The enzyme nitrile hydratase (NHase) catalyzes hydration of organic nitriles to the corresponding amides. It contains either a non-heme Fe(III) or a non-corrinoid Co(III) center at the active site. The coordination structure around the M(III) (M = Fe, Co) center at the active-site comprises several unusual features that raised a high level of curiosity among bioinorganic chemists. Such features include (a) direct coordination of two deprotonated carboxamido-N donors and (b) two out of three coordinated Cys-S centers post-translationally oxygenated to cysteine-sulfenato and cysteine sulfinito moieties. In addition, the inactive (dark) form of Fe-NHase contains a bound NO at the sixth site that is replaced by water upon illumination. A metal-bound hydroxide appears to be responsible for the hydration of the nitrile substrates. Systematic synthetic analogue approach and theoretical studies have been employed to unravel the roles of these unusual coordination features of the active site of NHase. Research results from several laboratories have established a good structure–function correlation in NHase. The correlation provides clear understanding of nature’s choice for such atypical coordination features in NHase and underscores the potential of molecular design in bioinorganic chemistry.