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Publication Abstract from PubMed

The catalytic activity of the pyridoxal 5'-phosphate-dependent tryptophan synthase alpha(2)beta(2) complex is allosterically regulated. The hydrogen bond between the helix betaH6 residue betaSer(178) and the loop alphaL6 residue Gly(181) was shown to be critical in ligand-induced intersubunit signaling, with the alpha-beta communication being completely lost in the mutant betaSer(178) --> Pro (Marabotti, A., De Biase, D., Tramonti, A., Bettati, S., and Mozzarelli, A. (2001) J. Biol. Chem. 276, 17747-17753). The structural basis of the impaired allosteric regulation was investigated by determining the crystal structures of the mutant betaSer(178) --> Pro in the absence and presence of the alpha-subunit ligands indole-3-acetylglycine and glycerol 3-phosphate. The mutation causes local and distant conformational changes especially in the beta-subunit. The ligand-free structure exhibits larger differences at the N-terminal part of helix betaH6, whereas the enzyme ligand complexes show differences at the C-terminal side. In contrast to the wild-type enzyme loop alphaL6 remains in an open conformation even in the presence of alpha-ligands. This effects the equilibrium between active and inactive conformations of the alpha-active site, altering k(cat) and K(m), and forms the structural basis for the missing allosteric communication between the alpha- and beta-subunits.

Crystal structure of the beta Ser178--> Pro mutant of tryptophan synthase. A "knock-out" allosteric enzyme.,Weyand M, Schlichting I, Herde P, Marabotti A, Mozzarelli A J Biol Chem. 2002 Mar 22;277(12):10653-60. Epub 2001 Dec 26. PMID:11756454^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.