Methylidene-imidazolone: a novel electrophile for substrate activation

The recent three-dimensional structure of histidine ammonialyase revealed t hat the enzyme contains a 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) ring, which forms autocatalytically from an Ala-Ser143-Gly triad. This nov el prosthetic group, which is also present in phenylalanine ammonia-lyase, activates substrates by electrophilic interaction. Modern analytical method s, theoretical calculations and molecular biology tools have given further insight into the mode of action of MIO.