An Unusual Cation-Binding Site and Distinct Domain-Domain Interactions Distinguish Class II Enolpyruvylshikimate-3-phosphate Synthases

Biochemistry
Samuel H LightWayne F Anderson

Abstract

Enolpyruvylshikimate-3-phosphate synthase (EPSPS) catalyzes a critical step in the biosynthesis of a number of aromatic metabolites. An essential prokaryotic enzyme and the molecular target of the herbicide glyphosate, EPSPSs are the subject of both pharmaceutical and commercial interest. Two EPSPS classes that exhibit low sequence homology, differing substrate/glyphosate affinities, and distinct cation activation properties have previously been described. Here, we report structural studies of the monovalent cation-binding class II Coxiella burnetii EPSPS (cbEPSPS). Three cbEPSPS crystal structures reveal that the enzyme undergoes substantial conformational changes that alter the electrostatic potential of the active site. A complex with shikimate-3-phosphate, inorganic phosphate (Pi), and K(+) reveals that ligand induced domain closure produces an unusual cation-binding site bordered on three sides by the N-terminal domain, C-terminal domain, and the product Pi. A crystal structure of the class I Vibrio cholerae EPSPS (vcEPSPS) clarifies the basis of differential class I and class II cation responsiveness, showing that in class I EPSPSs a lysine side chain occupies the would-be cation-binding site. Finally, we identify distinc...Continue Reading

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Citations

Apr 27, 2018·Biotechnology Journal·Bernhard SchoenenbergerRoland Wohlgemuth
Jan 23, 2019·Environmental Microbiology·Dennis WickeFabian M Commichau
Apr 17, 2019·PloS One·Nicolas BlotHélène Delatte
Jun 6, 2019·MBio·Rita V M RioBrian L Weiss
Jul 15, 2017·Frontiers in Cellular and Infection Microbiology·Ina HäusleinWolfgang Eisenreich
Dec 25, 2019·Scientific Reports·Marjo HelanderIrma Saloniemi
Aug 24, 2017·Biochemical and Biophysical Research Communications·Jun Hyuck LeeHak Jun Kim

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