Analysis of fluoromethyl group chirality establishes a common stereochemical course for the enolpyruvyl transfers catalyzed by EPSP synthase and UDP-GlcNAc enolpyruvyl transferase

Biochemistry
D H KimC T Walsh

Abstract

The stereochemistry of transient methyl group formation at C-3 of phosphoenolpyruvate (PEP) in the reaction catalyzed by 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase has been examined using the pseudosubstrates, (E)- and (Z)-3-fluorophosphoenolpyruvate (FPEP). Kinetically stable, chiral [1H, 2H]fluoromethyl analogs of the reaction tetrahedral intermediate were isolated and subjected to decomposition and stereochemical analysis. EPSP synthase was found to catalyze the 2-re face addition of solvent-derived hydrogen to C-3 of FPEP (corresponding to the 2-si face of PEP). Comparison of these data with prior analogous work on the MurA reaction [Kim, D.H., Lees, W.J., & Walsh, C. T. (1995) J. Am. Chem. Soc. 117, 6380-6381] suggests that the two enolpyruvyl transferases share a common stereochemical course, further strengthening the mechanistic, structural, and evolutionary relationship between the two enzymes.

Citations

Jul 7, 2012·Journal of the American Chemical Society·Meiyan LouPaul J Berti
Jun 27, 2002·European Journal of Biochemistry·Luis Fernando García-Alles, Bernhard Erni
Mar 12, 2004·Annual Review of Plant Physiology and Plant Molecular Biology·Klaus M. Herrmann, Lisa M. Weaver
Jun 13, 2013·The Journal of Antibiotics·Christopher T Walsh, Timothy A Wencewicz
Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·E SchönbrunnW Kabsch
Dec 5, 2006·Anais Da Academia Brasileira De Ciências·Luiz F L ReisMauro M Teixeira
Dec 14, 2001·The Journal of Biological Chemistry·Luis Fernando Garcia-AllesBernhard Erni

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