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Structure of Klebsiella pneumoniae adenosine monophosphate nucleosidase

Brian C Richardson1, Roger Shek2, Wesley C Van Voorhis2

  • 1The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America.

Plos One
|October 20, 2022
PubMed

Insights

Klebsiella pneumoniae adenosine monophosphate nucleosidase (KpAmn) structure was determined using cryo-EM. This bacterial enzyme is a potential target for novel antibiotics against drug-resistant infections.

Area of Science:

  • Microbiology
  • Structural Biology
  • Drug Discovery

Background:

  • Klebsiella pneumoniae is a significant cause of hospital-acquired infections, including pneumonia and sepsis.
  • Increasing antibiotic resistance in K. pneumoniae necessitates the development of novel therapeutic strategies.
  • Enzymes in purine metabolism are promising targets for new antibacterial agents.

Purpose of the Study:

  • To determine the structure of K. pneumoniae adenosine monophosphate nucleosidase (KpAmn) using cryo-electron microscopy.
  • To provide a structural basis for the development of novel antibiotics targeting KpAmn.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was employed to elucidate the structure of KpAmn.
  • Comparative structural analysis was performed against homologous prokaryotic proteins.

Main Results:

  • The structure revealed a conserved fold and a hexameric assembly for KpAmn.
  • Key active site residues were identified, along with differences in distal loops compared to crystal structures.
  • This is the first cryo-EM structure reported for any Adenosine Monophosphate Nucleosidase (Amn) enzyme.

Conclusions:

  • The determined KpAmn structure provides crucial insights for structure-guided drug development.
  • This work advances the structural understanding of Amn enzymes in clinically relevant bacteria.
  • Targeting KpAmn offers a potential avenue for combating antibiotic-resistant K. pneumoniae infections.

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