The molecular pathway for the allosteric regulation of tryptophan synthase.
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 alpha loop6 Gly(181) and beta helix6 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 beta Ser(178)Pro mutant, in the absence and presence of alpha-subunit ligands, indicates that the removal of the interaction between beta Ser(178) and alpha Gly(181) strongly affects the equilibrium between active (closed) and inactive (open) conformations of the alpha-active site, the latter being stabilized in both mutants.
Raboni
Samanta
S
Department of Biochemistry and Molecular Biology, University of Parma, Parma 43100, Italy.
Pioselli
Barbara
B
Bettati
Stefano
S
Mozzarelli
Andrea
A
D000494:Allosteric Regulation; D006860:Hydrogen Bonding; D011487:Protein Conformation; D021122:Protein Subunits; D014367:Tryptophan Synthase / Q000737:chemistry* / Q000378:metabolism
D021122:Protein Subunits; D014367:Tryptophan Synthase