Crystal structure of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase from the ESKAPE pathogen Acinetobacter baumannii.

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 (AbEPSP) 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.

• Authors: Kristin A Sutton, Jennifer Breen, Thomas A Russo, L Wayne Schultz, Timothy C Umland
• Journal: Acta crystallographica. Section F, Structural biology communications (Acta Crystallogr F Struct Biol Commun) Vol. 72 Issue Pt 3 Pg. 179-87 (Mar 2016) ISSN: 2053-230X [Electronic] United States
• PMID: 26919521 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Bacterial Proteins
• Shikimic Acid
• shikimic acid-3-phosphate
• 3-Phosphoshikimate 1-Carboxyvinyltransferase

Topics

• 3-Phosphoshikimate 1-Carboxyvinyltransferase (chemistry)
• Acinetobacter baumannii (enzymology)
• Amino Acid Sequence
• Bacterial Proteins (chemistry)
• Catalytic Domain
• Crystallization
• Crystallography, X-Ray
• Models, Molecular
• Protein Conformation, alpha-Helical
• Shikimic Acid (analogs & derivatives, chemistry)