This family includes phenylalanine ammonia-lyase, (PAL; ), histidine ammonia-lyase, (HAL; ), and tyrosine aminomutase, () [, , ].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 []. 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 []. Tyrosine 2,3-aminomutase has aminomutase activity and, to a much lesser extent, ammonia-lyase activity [].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 [, , , ].
This domain is found in eukaryotes and is about 150 amino acids in length. It has a conserved GILD sequence motif. Some proteins containing this domain are essential for cell polarity establishment and maintenance such as Par3 (partitioning defective), and some are involved in conversion of histidine into ammonia (a crucial step for forming histamine in humans) such as Histidine ammonia lyase (HAL). This N-terminal domain is found to mediate oligomerization critical for the membrane localization of Par-3. It is also found to possess a self-association capacity via a front-to-back mode in Par-3 and HAL proteins. However, unlike the Par-3 N-terminal domain which self-assembles into a left-handed helical filament, the HAL N-terminal domain does not tend to form a helical filament but rather self-assembles into circular oligomeric particles. This has been suggested to be likely due to the absence of equivalent charged residues that are essential for the longitudinal packing of the Par-3 N-terminal domain filament [].
This entry represents the active site of phenylalanine ammonia-lyase (PAL; ) and the mechanistically related protein histidine ammonia lyase (HAL; ). Both contain a catalytic Ala-Ser-Gly triad that is post-translationally cyclised []. 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. PAL catalyses the removal of an ammonia group from phenylalanine to form trans-cinnamate. 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 [].The two types of enzymes are functionally and structurally related []. They are the only enzymes which are known to have the modified amino acid dehydro-alanine (DHA) in their active site. A serine residue has been shown [, , ]to be the precursor of this essential electrophilic moiety. The region around the active site serine is well conserved and has been used as the signature pattern for this entry.
