Methylidene-Imidazolone (MIO) from histidine and phenylalanine ammonia-lyase

Abstract

Publisher Summary This chapter discusses the history, discovery, structure, reactivity, and catalytic role of the Methylidene-Imidazolone (MIO) group in two ammonia-lyase reactions. Enzymes, however, take advantage also of electrophilic catalysis. In addition to the use of protons as electrophile, they often use cofactors, such as pyridoxal phosphate, the classical electrophilic cocatalyst. Alternatively, the catalytically essential electrophilic group may be generated by post-translational modification of an amino acid side chain. Two such modifications of the serine side chain are known: (1) Dehydration coupled with the removal of an N-terminal peptide portion leads to an N-terminal pyruvyl group (Snell, 1986). (2) Cyclization of the internal tripeptide AlaSerGly concomitant with the elimination of two molecules of water. The latter leads to the highly electrophilic 4-methylidene- imidazol-5-one (MIO) prosthetic group (Schwede et al., 1999). Although the pyruvyl group is involved in similar catalytic processes as pyridoxal phosphate and may be its primitive precursor in evolution (Snell, 1986), the MIO group participates in chemically unique ammonia eliminations catalyzed by the enzymes histidine and phenylalanine ammonia-lyases.