Spatial structure and the mechanism of tyrosine phenol-lyase and tryptophan indole-lyase

Bacterial tyrosine phenol-lyase [EC 4.1.99.2] and tryptophan indole-lyase [EC 4.1.99.1] are pyridoxal 5′-phosphate dependent β-eliminating lyases that catalyze the reversible decomposition of L-tyrosine and L-tryptophan to pyruvate, ammonia, and phenol or indole, respectively. This review considers the three-dimensional structures of the holoenzymes of tyrosine phenol-lyase and tryptophan indole-lyase and several enzyme-inhibitor complexes that model distinct reaction stages of the β-elimination of L-tyrosine. The structural basis of the influence of monovalent cations on enzymatic activity is discussed. Studies of the spectral and catalytic properties of mutant enzymes made it possible to elucidate the catalytic functions of a number of amino acid residues and to conclude that the acid-base properties of the catalytic groups are optimal for catalysis in the hydrophobic active sites of tyrosine phenol-lyase and tryptophan indol-lyase and differ from those in water solutions. A study of the mechanisms of labilization of the Cα proton of the bound amino acids and activation of the leaving groups of the substrates during the catalytic process demonstrated that the reaction proceeds via concerted, rather than stepwise, pathways in certain cases.