1K8Z

CRYSTAL STRUCTURE OF THE TRYPTOPHAN SYNTHASE BETA-SER178PRO MUTANT COMPLEXED WITH N-[1H-INDOL-3-YL-ACETYL]GLYCINE ACID

Summary for 1K8Z

• Entry DOI: 10.2210/pdb1k8z/pdb
• Related: 1K7X 1K8Y
• Descriptor: TRYPTOPHAN SYNTHASE ALPHA CHAIN, TRYPTOPHAN SYNTHASE BETA CHAIN, N-[1H-INDOL-3-YL-ACETYL]GLYCINE ACID, ... (6 entities in total)
• Functional Keywords: carbon-oxygen lyase, tryptophan biosynthesis, pyridoxal phosphate, lyase
• Biological source: Salmonella typhimurium; More
• Total number of polymer chains: 2
• Total formula weight: 71998.89

Authors

Weyand, M.,Schlichting, I.,Marabotti, A.,Mozzarelli, A. (deposition date: 2001-10-26, release date: 2002-06-19, Last modification date: 2023-08-16)

Primary citation

Weyand, M.,Schlichting, I.,Herde, P.,Marabotti, A.,Mozzarelli, A.
Crystal structure of the beta Ser178--> Pro mutant of tryptophan synthase. A "knock-out" allosteric enzyme.
J.Biol.Chem., 277:10653-10660, 2002

PubMed 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 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.

PubMed: 11756454
DOI: 10.1074/jbc.M111031200

Experimental method

X-RAY DIFFRACTION (1.7 Å)