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The L-Rhamnose Biosynthetic Pathway in Trichomonas vaginalis : Identification and Characterization of UDP-D-Glucose 4,6-dehydratase.

Matteo GaglianoneMaria Elena LaugieriAdriana Lucely RojasMaria Rosaria CoppolaFrancesco PiacentePier Luigi FioriMichela Giulia Tonetti
Published in: International journal of molecular sciences (2022)
Trichomonas vaginalis is the causative agent of one of the most widespread sexually transmitted diseases in the world. The adhesion of the parasite to the vaginal epithelial cells is mediated by specific proteins and by a complex glycan structure, the lipoglycan (TvLG), which covers the pathogen surface. L-rhamnose is an important component of TvLG, comprising up to 40% of the monosaccharides. Thus, the inhibition of its production could lead to a severe alteration in the TvLG structure, making the L-rhamnose biosynthetic pathway an attractive pharmacologic target. We report the identification and characterization of the first committed and limiting step of the L-rhamnose biosynthetic pathway, UDP-D-glucose 4,6-dehydratase (UGD, EC 4.2.1.76). The enzyme shows a strong preference for UDP-D-glucose compared to dTDP-D-glucose; we propose that the mechanism underlying the higher affinity for the UDP-bound substrate is mediated by the differential recognition of ribose versus the deoxyribose of the nucleotide moiety. The identification of the enzymes responsible for the following steps of the L-rhamnose pathway (epimerization and reduction) was more elusive. However, sequence analyses suggest that in T. vaginalis L-rhamnose synthesis proceeds through a mechanism different from the typical eukaryotic pathways, displaying intermediate features between the eukaryotic and prokaryotic pathways and involving separate enzymes for the epimerase and reductase activities, as observed in bacteria. Altogether, these results form the basis for a better understanding of the formation of the complex glycan structures on TvLG and the possible use of L-rhamnose biosynthetic enzymes for the development of selective inhibitors.
Keyphrases
  • blood glucose
  • type diabetes
  • high resolution
  • adipose tissue
  • blood pressure
  • pseudomonas aeruginosa
  • escherichia coli
  • toxoplasma gondii
  • amino acid
  • candida albicans
  • cell surface
  • staphylococcus aureus