1K7F

CRYSTAL STRUCTURE OF WILD-TYPE TRYPTOPHAN SYNTHASE COMPLEXED WITH N-[1H-INDOL-3-YL-ACETYL]VALINE ACID

Summary for 1K7F

• Entry DOI: 10.2210/pdb1k7f/pdb
• Related: 1K3U 1K7E
• Descriptor: TRYPTOPHAN SYNTHASE ALPHA CHAIN, TRYPTOPHAN SYNTHASE BETA CHAIN, N-[1H-INDOL-3-YL-ACETYL]VALINE ACID, ... (5 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: 72007.94

Authors

Weyand, M.,Schlichting, I.,Marabotti, A.,Mozzarelli, A. (deposition date: 2001-10-19, release date: 2002-07-10, Last modification date: 2023-08-16)

Primary citation

Weyand, M.,Schlichting, I.,Marabotti, A.,Mozzarelli, A.
Crystal structures of a new class of allosteric effectors complexed to tryptophan synthase.
J.Biol.Chem., 277:10647-10652, 2002

PubMed Abstract: 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 alpha-subunit reaction.

PubMed: 11756456
DOI: 10.1074/jbc.M111285200

Experimental method

X-RAY DIFFRACTION (1.9 Å)