Structural determinants and modulation of substrate specificity in phenylalanine-tyrosine ammonia-lyases

Gordon V. Louie, Marianne E. Bowman, Michelle C. Moffitt, T. J. Baiga, Bradley S. Moore, Joseph P. Noel

    Research output: Contribution to journalArticle

    122 Citations (Scopus)

    Abstract

    Aromatic amino acid ammonia-lyases catalyze the deamination of L-His, L-Phe, and L-Tyr, yielding ammonia plus aryl acids bearing an α,β-unsaturated propenoic acid. We report crystallographic analyses of unliganded Rhodobacter sphaeroides tyrosine ammonia-lyase (RsTAL) and RsTAL bound to p-coumarate and caffeate. His 89 of RsTAL forms a hydrogen bond with the p-hydroxyl moieties of coumarate and caffeate. His 89 is conserved in TALs but replaced in phenylalanine ammonia-lyases (PALs) and histidine ammonia-lyases (HALs). Substitution of His 89 by Phe, a characteristic residue of PALs, yields a mutant with a switch in kinetic preference from L-Tyr to L-Phe. Structures of the H89F mutant in complex with the PAL product, cinnamate, or the PAL-specific inhibitor, 2-aminoindan-2-phosphonate (AIP), support the role of position 89 as a specificity determinant in the family of aromatic amino acid ammonia-lyases and aminomutases responsible for β-amino acid biosynthesis.
    Original languageEnglish
    JournalChemistry and Biology
    Publication statusPublished - 2006

    Keywords

    • amino acids
    • structural determinants

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