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Crystal structure of the βSer178 -> Pro mutant of tryptophan synthase - A "knock-out" allosteric enzyme

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Weyand,  Michael
Max Planck Institute of Molecular Physiology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons98726

Schlichting,  Ilme
Abt. III: Physikalische Biochemie, Max Planck Institute of Molecular Physiology, Max Planck Society;

Herde,  Petra
Max Planck Institute of Molecular Physiology, Max Planck Society;

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Citation

Weyand, M., Schlichting, I., Herde, P., Marabotti, A., & Mozzarelli, A. (2002). Crystal structure of the βSer178 -> Pro mutant of tryptophan synthase - A "knock-out" allosteric enzyme. Journal of Biological Chemistry, 277(12): 1, pp. 10653-10660. Retrieved from http://www.jbc.org/cgi/reprint/277/12/10653.pdf.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0014-0EB6-1
Abstract
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 inter-subunit 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 a-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.