Crystal structure of 5‐enolpyruvylshikimate‐3‐phosphate (EPSP) synthase from the ESKAPE pathogen Acinetobacter baumannii. Issue 3 (2nd March 2016)

• Record Type: Journal Article
• Authors: Sutton, Kristin A.; Breen, Jennifer; Russo, Thomas A.; Schultz, L. Wayne; Umland, Timothy C.
• Is Part Of: Acta crystallographica. Volume 72:Issue 3(2016:Mar.)
• Page Start: 179
• Page End: 187
• Publication Date: 2016-03-02
• Subjects: shikimate pathway -- Acinetobacter baumannii -- essential genes -- antibiotic targets -- multidrug resistance -- EPSP synthase; Crystallography -- Periodicals; Crystals -- Periodicals; 548
• DOI: 10.1107/S2053230X16001114
• Languages: English
• ISSNs: 2053-230X

Abstract

Abstract : The crystal structure of 5‐enolpyruvylshikimate‐3‐phosphate (EPSP) synthase, a component of the shikimate pathway, was determined during its evaluation as a target for new antimicrobials effective against multidrug‐resistant, extensively drug‐resistant and pan‐drug‐resistant A. baumannii . This enzyme is essential for the growth and survival of this clinically important pathogen during host infection. Abstract : The enzyme 5‐enolpyruvylshikimate‐3‐phosphate (EPSP) synthase catalyzes the sixth step of the seven‐step shikimate pathway. Chorismate, the product of the pathway, is a precursor for the biosynthesis of aromatic amino acids, siderophores and metabolites such as folate, ubiquinone and vitamin K. The shikimate pathway is present in bacteria, fungi, algae, plants and apicomplexan parasites, but is absent in humans. The EPSP synthase enzyme produces 5‐enolpyruvylshikimate 3‐phosphate and phosphate from phosphoenolpyruvate and shikimate 3‐phosphate via a transferase reaction, and is the target of the herbicide glyphosate. The Acinetobacter baumannii gene encoding EPSP synthase, aroA, has previously been demonstrated to be essential during host infection for the growth and survival of this clinically important drug‐resistant ESKAPE pathogen. Prephenate dehydrogenase is also encoded by the bifunctional A. baumannii aroA gene, but its activity is dependent upon EPSP synthase since it operates downstream of the shikimate pathway. As part of an effort to evaluate new antimicrobial targets, recombinant A. baumannii EPSP (Ab EPSP) synthase, comprising residues Ala301–Gln756 of the aroA gene product, was overexpressed in Escherichia coli, purified and crystallized. The crystal structure, determined to 2.37 Å resolution, is described in the context of a potential antimicrobial target and in comparison to EPSP synthases that are resistant or sensitive to the herbicide glyphosate.