InterPro domain: IPR023144

The ubiquitous higher plant enzyme phenylalanine ammonia-lyase (PAL; 4.3.1.24 ) is a key biosynthetic catalyst in phenylpropanoid assembly. PAL catalyses the non-oxidative deamination of L-phenylalanine to trans-cinnamic acid. PAL contains a catalytic Ala-Ser-Gly triad that is post-translationally cyclised. PAL is structurally similar to the mechanistically related histidine ammonia lyase (HAL; 4.3.1.3 ), with PAL having an additional approximately 160 residues extending from the common fold [ 1 ]. Catalysis in PAL may be governed by the dipole moments of seven alpha helices associated with the PAL active site. The cofactor 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) resides atop the positive poles of three helices, for increasing its electrophillicity. Plant and fungal PAL enzymes contain aa approximately 100-residue long C-terminal multi-helix domain, which might play a role in the rapid response of PAL in the regulation of phenylpropanoid biosynthesis by destabilising the enzyme [ 2 ]. This entry also includes fungal proteins such as Phenylalanine ammonia-lyase CLZ10 which mediates the biosynthesis of squalestatin S1 with potent cholesterol lowering activity by targeting squalene synthase (SS) [ 3 ], and Phenylalanine ammonia-lyase hkm12 involved in the biosynthesis of hancockiamides, an unusual new family of N-cinnamoylated piperazines [ 4 ].

This superfamily represents the shielding domain at the C-terminal of PAL which is tightly connected to the core domain through the exceptionally long 55-residue helix alpha-17. The shielding domain restricts the access to the active centre so that the risk of inactivation by nucleophiles in conjunction with dioxygen is minimised. This may help PAL to function, for instance, in stressed plant tissue. It should be noted that PAL forms its electrophilic prosthetic group autocatalytically from its own polypeptide, rendering it independent of any cofactor and thus facilitating its upregulation [ 5 ].

1. Crystal structure of phenylalanine ammonia lyase: multiple helix dipoles implicated in catalysis. Biochemistry 43, 11403-16
2. 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
3. Identification and Heterologous Production of a Benzoyl-Primed Tricarboxylic Acid Polyketide Intermediate from the Zaragozic Acid A Biosynthetic Pathway. Org Lett 19, 3560-3563
4. Hancockiamides: phenylpropanoid piperazines from Aspergillus hancockii are biosynthesised by a versatile dual single-module NRPS pathway. Org Biomol Chem 19, 587-595
5. Structural basis for the entrance into the phenylpropanoid metabolism catalyzed by phenylalanine ammonia-lyase. Plant Cell 16, 3426-36