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Eukaryotic UDP-Galactopyranose Mutase (GLF Gene) in Microbial (2005)
BibTeX
@MISC{Doering05eukaryoticudp-galactopyranose,
author = {Tamara L. Doering and Victoria C. Jones and Michael R. Mcneil},
title = {Eukaryotic UDP-Galactopyranose Mutase (GLF Gene) in Microbial},
year = {2005}
}
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Abstract
Galactofuranose (Galf) 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 pro-karyotes, Galf is synthesized as the nucleotide sugar UDP-Galf 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 Galf 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 Galf synthesis may occur more broadly in eukaryotes than previously supposed. Overall, GLF/Galf synthesis in eukaryotes appears to occur with a disjunct distribution and often in pathogenic species, similar to what is seen
Keyphrases
glf gene eukaryotic udp-galactopyranose mutase ugm activity galf synthesis substrate-binding site pathogenic microbe algal phleovirus feldmannia irregularis novel sugar absent candidate eukaryotic glfs udp-galactopyranose mutase limited conservation pathogenic specie disjunct distribution combinatorial bioinformatics screen strong glf homologs nucleotide sugar prokaryotic glfs flavin adenine dinucleotide infectious cycle cryptococcus neoformans trypanosoma cruzi gene glf escherichia coli critical role eukaryotic glfs caenorhabditis elegans alga chlamydomonas glf phylogenetic distribution cell surface formation key residue urochordate halocynthia glf galf synthesis elegans open reading frame core residue parasitic nematode
