InterPro domain: IPR001106

PAL and HAL are members of the Lyase class I_like superfamily of enzymes that, catalyze similar beta-elimination reactions and are active as homotetramers. Both PAL and HAL contain a catalytic Ala-Ser-Gly triad that is post-translationally cyclised [ 1 ]. PAL is a key biosynthetic catalyst in phenylpropanoid assembly in plants and fungi, and is involved in the biosynthesis of a wide variety of secondary metabolites such as flavanoids, furanocoumarin phytoalexins and cell wall components. These compounds are important for normal growth and in responses to environmental stress. HAL catalyses the first step in histidine degradation, the removal of an ammonia group from histidine to produce urocanic acid. The core domain in PAL and HAL share about 30% sequence identity, with PAL containing an additional approximately 160 residues extending from the common fold [ 2 ]. Tyrosine 2,3-aminomutase has aminomutase activity and, to a much lesser extent, ammonia-lyase activity [ 3 ].

This family includes phenylalanine ammonia-lyase, (PAL; 4.3.1.24 ), histidine ammonia-lyase, (HAL; 4.3.1.3 ), and tyrosine aminomutase, ( 5.4.3.6 ) [ 4 , 5 , 6 ].

PAL is being explored as enzyme substitution therapy for Phenylketonuria (PKU), a disorder which involves an inability to metabolize phenylalanine. HAL failure in humans results in the disease histidinemia [ 7 , 8 , 9 , 10 ].

1. The essential tyrosine-containing loop conformation and the role of the C-terminal multi-helix region in eukaryotic phenylalanine ammonia-lyases. FEBS J. 273, 1004-19
2. Crystal structure of phenylalanine ammonia lyase: multiple helix dipoles implicated in catalysis. Biochemistry 43, 11403-16
3. Discovery of additional members of the tyrosine aminomutase enzyme family and the mutational analysis of CmdF. Chembiochem 10, 741-50
4. Structural and catalytic properties of the four phenylalanine ammonia-lyase isoenzymes from parsley (Petroselinum crispum Nym.). Eur. J. Biochem. 225, 491-9
5. Crystal structure of histidine ammonia-lyase revealing a novel polypeptide modification as the catalytic electrophile. Biochemistry 38, 5355-61
6. Molecular and biochemical studies of chondramide formation-highly cytotoxic natural products from Chondromyces crocatus Cm c5. Chem. Biol. 13, 667-81
7. Methylidene-imidazolone: a novel electrophile for substrate activation. Curr Opin Chem Biol 5, 512-24
8. Plant-like biosynthetic pathways in bacteria: from benzoic acid to chalcone. J. Nat. Prod. 65, 1956-62
9. Mechanisms of inhibition of phenylalanine ammonia-lyase by phenol inhibitors and phenol/glycine synergistic inhibitors. Arch. Biochem. Biophys. 412, 170-5
10. Structures of two histidine ammonia-lyase modifications and implications for the catalytic mechanism. Eur. J. Biochem. 269, 1790-7