Crystal structure of the bifunctional chorismate synthase from Saccharomyces cerevisiae |
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Authors: | Quevillon-Cheruel Sophie Leulliot Nicolas Meyer Philippe Graille Marc Bremang Michael Blondeau Karine Sorel Isabelle Poupon Anne Janin Joël van Tilbeurgh Herman |
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Institution: | Institut de Biochimie et de Biophysique Moléculaire et Cellulaire (CNRS-UMR 8619), Université Paris-Sud, Batiment 430, 91405 Orsay, France. |
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Abstract: | Chorismate synthase (EC 4.2.3.5), the seventh enzyme in the shikimate pathway, catalyzes the transformation of 5-enolpyruvylshikimate 3-phosphate (EPSP) to chorismate, which is the last common precursor in the biosynthesis of numerous aromatic compounds in bacteria, fungi, and plants. The chorismate synthase reaction involves a 1,4-trans-elimination of phosphoric acid from EPSP and has an absolute requirement for reduced FMN as a cofactor. We have determined the three-dimensional x-ray structure of the yeast chorismate synthase from selenomethionine-labeled crystals at 2.2-A resolution. The structure shows a novel betaalphabetaalpha fold consisting of an alternate tight packing of two alpha-helical and two beta-sheet layers, showing no resemblance to any documented protein structure. The molecule is arranged as a tight tetramer with D2 symmetry, in accordance with its quaternary structure in solution. Electron density is missing for 23% of the amino acids, spread over sequence regions that in the three-dimensional structure converge on the surface of the protein. Many totally conserved residues are contained within these regions, and they probably form a structured but mobile domain that closes over a cleft upon substrate binding and catalysis. This hypothesis is supported by previously published spectroscopic measurements implying that the enzyme undergoes considerable structural changes upon binding of both FMN and EPSP. |
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