Crystal structure of 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase from the ESKAPE pathogen Acinetobacter baumannii
| Autor: | Thomas A. Russo, Timothy C. Umland, Jennifer Breen, K.A. Sutton, L. Wayne Schultz |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Acinetobacter baumannii Models Molecular Protein Conformation alpha-Helical 030106 microbiology Biophysics Shikimic Acid Crystallography X-Ray Biochemistry Microbiology Research Communications 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Structural Biology Catalytic Domain Genetics Aromatic amino acids Shikimate pathway Amino Acid Sequence biology Aroa Prephenate dehydrogenase EPSP synthase Shikimic acid Condensed Matter Physics biology.organism_classification 3-Phosphoshikimate 1-Carboxyvinyltransferase chemistry Crystallization |
| Popis: | 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-phosphateviaa transferase reaction, and is the target of the herbicide glyphosate. TheAcinetobacter baumanniigene 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 bifunctionalA. baumannii aroAgene, 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, recombinantA. baumanniiEPSP (AbEPSP) synthase, comprising residues Ala301–Gln756 of thearoAgene product, was overexpressed inEscherichia 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. |
| Databáze: | OpenAIRE |
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