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Visualization of ATP Synthase Dimers in Mitochondria by Electron Cryo-tomography
10:39

Visualization of ATP Synthase Dimers in Mitochondria by Electron Cryo-tomography

Published on: September 14, 2014

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Structure of 2-keto-3-deoxy-D-manno-octulosonate-8-phosphate synthase from Pseudomonas aeruginosa

Sarah K Nelson1, Alan Kelleher, Gonteria Robinson

  • 1National School of Tropical Medicine, Baylor College of Medicine, 1102 Bates Avenue, Houston, TX 77030, USA.

Acta Crystallographica. Section F, Structural Biology and Crystallization Communications
|October 9, 2013
PubMed

Insights

Structural studies of Pseudomonas aeruginosa 2-keto-3-deoxy-D-manno-octulosonate-8-phosphate synthase (KDO8Ps) are crucial for developing new antibiotics. The crystal structure reveals a TIM-barrel fold, offering insights into lipopolysaccharide synthesis inhibition.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Microbiology

Background:

  • Pseudomonas aeruginosa is an opportunistic pathogen known for antibiotic resistance.
  • Developing novel antibiotics targeting essential bacterial enzymes absent in mammals is a priority.
  • 2-Keto-3-deoxy-D-manno-octulosonate-8-phosphate synthase (KDO8Ps) is vital for P. aeruginosa survival and virulence.

Purpose of the Study:

  • To initiate structural studies of KDO8Ps from P. aeruginosa.
  • To understand the enzyme's structure for potential drug development targeting lipopolysaccharide synthesis.

Main Methods:

  • Recombinant expression and purification of P. aeruginosa KDO8Ps.
  • X-ray crystallography to determine the enzyme's three-dimensional structure.
  • Crystallization achieved using vapor diffusion with phosphoenolpyruvate.

Main Results:

  • The crystal structure of P. aeruginosa KDO8Ps was determined.
  • The enzyme exhibits a canonical α/β TIM-barrel fold.
  • A tetrameric quaternary structure was observed within the asymmetric unit.

Conclusions:

  • The determined structure provides a foundation for designing inhibitors of KDO8Ps.
  • Targeting KDO8Ps could lead to new antibiotics against P. aeruginosa.
  • Understanding LPS synthesis is key to combating Gram-negative bacterial infections.
Keywords:
2-dehydro-3-deoxyphosphooctonate aldolase3-deoxy-8-phosphooctulonate synthasealdolasesarabinose 5-phosphateeducation projectlipopolysaccharide biosynthesisphosphoenolpyruvate

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