The pyridoxal 5'-phosphate (PLP)-dependent tryptophan synthase is a alpha(2)beta(2) complex. The alpha-beta subunit interaction plays a critical role both in the reciprocal activation of the individual subunits and in the allosteric regulation. We have investigated whether mutations of alphaloop6 Gly(181) and betahelix6 Ser(178) affect intersubunit communication. The loss of the hydrogen bond between these residues, achieved by proline substitution, does not significantly influence the intersubunit catalytic activation, but completely abolishes ligand-induced intersubunit signaling. The comparison of the crystal structure of the wild type and betaSer(178) Pro mutant, in the absence and presence of alpha-subunit ligands, indicates that the removal of the interaction between betaSer(178) and alphaGly(181) strongly affects the equilibrium between active (closed) and inactive (open) conformations of the a-active site, the latter being stabilized in both mutants.
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