NDLI: Eukaryotic UDP-Galactopyranose Mutase (GLF Gene) in Microbial and Metazoal Pathogens†

Content Provider	PubMed Central
Author	Beverley, Stephen M. Owens, Katherine L. Showalter, Melissa Griffith, Cara L. Doering, Tamara L. Jones, Victoria C. Mcneil, Michael R.
Copyright Year	2005
Abstract	Galactofuranose (Gal f ) is a novel sugar absent in mammals but present in a variety of pathogenic microbes, often within glycoconjugates that play critical roles in cell surface formation and the infectious cycle. In prokaryotes, Gal f is synthesized as the nucleotide sugar UDP-Gal f by UDP-galactopyranose mutase (UGM) (gene GLF). Here we used a combinatorial bioinformatics screen to identify a family of candidate eukaryotic GLFs that had previously escaped detection. GLFs from three pathogens, two protozoa (Leishmania major and Trypanosoma cruzi) and one fungus (Cryptococcus neoformans), had UGM activity when expressed in Escherichia coli and assayed in vivo and/or in vitro. Eukaryotic GLFs are closely related to each other but distantly related to prokaryotic GLFs, showing limited conservation of core residues around the substrate-binding site and flavin adenine dinucleotide binding domain. Several eukaryotes not previously investigated for Gal f synthesis also showed strong GLF homologs with conservation of key residues. These included other fungi, the alga Chlamydomonas and the algal phleovirus Feldmannia irregularis, parasitic nematodes (Brugia, Onchocerca, and Strongyloides) and Caenorhabditis elegans, and the urochordates Halocynthia and Cionia. The C. elegans open reading frame was shown to encode UGM activity. The GLF phylogenetic distribution suggests that Gal f synthesis may occur more broadly in eukaryotes than previously supposed. Overall, GLF/Gal f synthesis in eukaryotes appears to occur with a disjunct distribution and often in pathogenic species, similar to what is seen in prokaryotes. Thus, UGM inhibition may provide an attractive drug target in those eukaryotes where Gal f plays critical roles in cellular viability and virulence.
Related Links	http://dx.doi.org/10.1128/ec.4.6.1147-1154.2005
Ending Page	1154
Page Count	8
Starting Page	1147
File Format	PDF
ISSN	15359778
e-ISSN	15359786
Journal	Eukaryotic Cell
Issue Number	6
Volume Number	4
Language	English
Publisher	American Society for Microbiology
Publisher Date	2005-06-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Molecular Biology Microbiology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Microbiology

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