Three-Dimensional Structure of the Bifunctional Enzyme N-(5′-phosphoribosyl)anthranilate Isomerase-indole-3-glycerol-phosphate Synthase from Escherichia coli

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 16; pp. 5690 - 5694
• Main Authors: Priestle, J. P., Grütter, M. G., White, J. L., Vincent, M. G., Kania, M., Wilson, E., Jardetzky, T. S., Kirschner, K., Jansonius, J. N.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.08.1987; National Acad Sciences
• Subjects: Active sites; Aldose-Ketose Isomerases; Amino Acid Sequence; Amino acids; Atoms; Binding Sites; Biochemistry; Biological and medical sciences; Carbohydrate Epimerases; Carboxy-Lyases; Crystalline structure; Crystals; Datasets; Diffractometers; Electrical phases; Enzymes; Escherichia coli; Escherichia coli - enzymology; Fundamental and applied biological sciences. Psychology; Indole-3-Glycerol-Phosphate Synthase; Macromolecular Substances; Molecular biophysics; Molecular Weight; Multienzyme Complexes; Peptide Mapping; Structure in molecular biology; Tryptophan - biosynthesis; X-Ray Diffraction; Enzyme; Escherichia coli; Tryptophan; Primary structure; Biosynthesis; Complexes; X ray diffraction; Spatial structure; Indole-3-glycerol-phosphate synthase; Molecular model; Bacteria; Escherichieae; Enterobacteriaceae; Crystalline structure
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.16.5690

N-(5′-Phosphoribosyl)anthranilate isomerase-indole-3-glycerol-phosphate synthase from Escherichia coli is a monomeric bifunctional enzyme of Mr 49,500 that catalyzes two sequential reactions in the biosynthesis of tryptophan. The three-dimensional structure of the enzyme has been determined at 2.8- angstrom resolution by x-ray crystallography. The two catalytic activities reside on distinct functional domains of similar folding, that of an eightfold parallel β -barrel with α -helices on the outside connecting the β -strands. Both active sites were located with an iodinated substrate analogue and found to be in depressions on the surface of the domains created by the outward-curving loops between the carboxyl termini of the β -sheet strands and the subsequent α -helices. They do not face each other, making ``channeling'' of the substrate between active sites virtually impossible. Despite the structural similarity of the two domains, no significant sequence homology was found when topologically equivalent residues were compared.