Structure and Function of Amino Acid Ammonia-lyases

Abstract

Histidine ammonia-lyase (HAL) and methylaspartate ammonia-lyase (MAL) belong to the family of carbon-nitrogen lyases (EC 4.3.1). The enzymes catalyze the α,β-elimination of ammonia from (S)-His to yield urocanic acid, and (S)-threo-(2S,3S)-3-methylaspartic acid to mesaconic acid, respectively. Based on structural analyses, the peptide at the active center of HAL from Pseudomonas putida is considered to be post-translationally dehydrated to form an electrophilic 4-methylidene-imidazole-one (MIO) group. A reaction mechanism was proposed with the structure. On the other hand, the structure of MAL from Citrobacter amalonaticus was found to be a typical TIM barrel structure with Mg2+ coordinated to the 4-carbonyl of the substrate methylaspartate. Unlike HAL, MIO was not observed in MAL, and the reaction of MAL appears to be completely different from phenylalanine ammonia-lyase (PAL), HAL, and other amino acid ammonia-lyases. A reaction mechanism is proposed in which the hydrogen at the β to the amino group of the substrate is abstracted forming an enolate type intermediate and then ammonia is released.