de.mpg.escidoc.pubman.appbase.FacesBean
Deutsch
 
Hilfe Wegweiser Impressum Kontakt Einloggen
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

Crystal structures of a new class of allosteric effectors complexed to tryptophan synthase

MPG-Autoren

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;

Externe Ressourcen
Es sind keine Externen Ressourcen verfügbar
Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Weyand, M., Schlichting, I., Marabotti, A., & Mozzarelli, A. (2002). Crystal structures of a new class of allosteric effectors complexed to tryptophan synthase. Journal of Biological Chemistry, 277(12): 1, pp. 10647-10652. Retrieved from http://www.jbc.org/cgi/reprint/277/12/10647.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0014-0EB8-E
Zusammenfassung
Tryptophan synthase is a bifunctional alpha(2)/beta(2) complex catalyzing the last two steps of L-tryptophan biosynthesis. The natural substrates of the alpha-subunit indole-3- glycerolphosphate and glyceraldehyde-3-phosphate, and the substrate analogs indole-3-propanolphosphate and DL-alpha- glycerol-3-phosphate are allosteric effectors of the beta- subunit activity. It has been shown recently, that the indole- 3-acetyl amino acids indole-3-acetylglycine and indole-3- acetyl-L-aspartic acid are both alpha-subunit inhibitors and beta-subunit allosteric effectors, whereas indole-3-acetyl-L- valine is only an alpha-subunit inhibitor (Marabotti, A., Cozzini, P., and Mozzarelli, A. (2000) Biochim. Biophys. Acta 1476, 287-299). The crystal structures of tryptophan synthase complexed with indole-3-acetylglycine and indole-3-acetyl-L- aspartic acid show that both ligands bind to the active site such that the carboxylate moiety is positioned similarly as the phosphate group of the natural substrates. As a consequence, the residues of the alpha-active site that interact with the ligands are the same as observed in the indole 3- glycerolphosphate-enzyme complex. Ligand binding leads to closure of loop alphaL6 of the alpha-subunit, a key structural element of intersubunit communication. This is in keeping with the allosteric role played by these compounds. The structure of the enzyme complex with indole-3-acetyl-L-valine is quite different. Due to the hydrophobic lateral chain, this molecule adopts a new orientation in the alpha-active site. In this case, closure of loop alphaL6 is no longer observed, in agreement with its functioning only as an inhibitor of the a- subunit reaction.