Cover picture: CMP-pseudaminic acid is a natural potent inhibitor of PseB, the first enzyme of the pseudaminic acid pathway in campylobacter jejuni and helicobacter pylori (chemmedchem 1/2008)

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1002/cmdc.200890000
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Name affiliation
  1. National Research Council of Canada. NRC Institute for Biological Sciences
FormatText, Article
Journal titleChemMedChem
ISSN1860-7179
1860-7187
Volume3
Issue1
Abstract
The cover picture shows the six enzymes (Pse B, C, H, G, I, F) responsible for producing CMP-pseudaminic acid (CMP-Pse) starting from UDP-GlcNAc in Campylobacter jejuni and Helicobacter pylori. These pathogens modify their flagella with sialic acid-like sugars such as pseudaminic acid (Pse) which are required for flagellar assembly, motility, and hence virulence. Pse B plays a central role in Pse biosynthesis and is also thought to be implicated in other glycan pathways making it a prime therapeutic target. Saturation transfer difference nuclear magnetic resonance spectroscopy (STD NMR) was used to determine binding epitopes for Pse B and to characterize Pse B inhibition with CMP-Pse at the molecular level. Docking studies and CORCEMA calculations validated STD NMR results and revealed that CMP-Pse and UDP-GlcNAc adopt similar conformations within the Pse B active site. These findings will guide the development of small-molecule inhibitors as a means to pharmaceutically control C. jejuni and H. pylori infections. For details, see the Communication by D. J. McNally, et al. on p. 55 ff.
Publication date
PublisherWiley
LanguageEnglish
Peer reviewedYes
NPARC number23002071
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