87664-40-2Relevant academic research and scientific papers
On the mechanism of chorismate mutases: Clues from wild-type E. coli enzyme and a site-directed mutant related to yeast; chorismate mutase
Galopin, Christophe C.,Zhang, Sheng,Wilson, David B.,Ganem, Bruce
, p. 8675 - 8678 (1996)
Thermodynamic parameters for E. coli chorismate mutase are reported. In addition, site-directed mutagenesis studies provide a direct mechanistic link to yeast chorismate mutase, further indicating the importance of entropic restriction and hydrogen bondin
When inhibitors do not inhibit: Critical evaluation of rational drug design targeting chorismate mutase from mycobacterium tuberculosis
Munack, Steffi,Leroux, Vincent,Roderer, Kathrin,?kvist, Mats,Van Eerde, André,Gundersen, Lise-Lotte,Krengel, Ute,Kast, Peter
, p. 2507 - 2527 (2013/01/16)
Tuberculosis (TB) is a devastating disease that claims millions of lives every year. Hindered access or non-compliance to medication, especially in developing countries, led to drug resistance, further aggravating the situation. With current standard ther
Isotope effects on the enzymatic and nonenzymatic reactions of chorismate
Wright, S. Kirk,Declue, Michael S.,Mandal, Ajay,Lee, Lac,Wiest, Olaf,Cleland, W. Wallace,Hilvert, Donald
, p. 12957 - 12964 (2007/10/03)
The important biosynthetic intermediate chorismate reacts thermally by two competitive pathways, one leading to 4-hydroxybenzoate via elimination of the enolpyruvyl side chain, and the other to prephenate by a facile Claisen rearrangement. Measurements with isotopically labeled chorismate derivatives indicate that both are concerted sigmatropic processes, controlled by the orientation of the enolpyruvyl group. In the elimination reaction of [4- 2H]chorismate, roughly 60% of the label was found in pyruvate after 3 h at 60 °C. Moreover, a 1.846 ± 0.057 2H isotope effect for the transferred hydrogen atom and a 1.0374 ± 0.0005 18O isotope effect for the ether oxygen show that the transition state for this process is highly asymmetric, with hydrogen atom transfer from C4 to C9 significantly less advanced than C-O bond cleavage. In the competing Claisen rearrangement, a very large 18O isotope effect at the bond-breaking position (1.0482 ± 0.0005) and a smaller 13C isotope effect at the bond-making position (1.0118 ± 0.0004) were determined. Isotope effects of similar magnitude characterized the transformations catalyzed by evolutionary unrelated chorismate mutases from Escherichia coli and Bacillus subtilis. The enzymatic reactions, like their solution counterpart, are thus concerted [3,3]-sigmatropic processes in which C-C bond formation lags behind C-O bond cleavage. However, as substantially larger 18O and smaller 13C isotope effects were observed for a mutant enzyme in which chemistry is fully rate determining, the ionic active site may favor a somewhat more polarized transition state than that seen in solution.
Uncatalyzed and chorismate mutase catalyzed claisen rearrangements of 5,6-dihydrochorismate and 6-Oxa-5,6-dihydrochorismate
Delany III, John J.,Padykula, Robert E.,Berchtold, Glenn A.
, p. 1394 - 1397 (2007/10/02)
The synthesis of 6-oxa-5,6-dihydrochorismic acid (4) from D-xylose is described. The half-lives for the uncatalyzed Claisen rearrangements of 5,6-dihydrochorismic acid (3) and 4 in D2O at 30 °C were 49000 and 1200 h, respectively, compared to a
