Essential Glycosyltransferases in Schizosaccharomyces Pombe

I cloned cDNAs encoding S. pombe, human and Caenorhabditis briggsiae Dol-P-Man synthases, all three of which lack a characteristic carboxy-terminal transmembrane region found on previously isolated Dol-P-Man synthases. Known Dol-P-Man synthases can therefore be divided into a 'human' or 'S. cerevisiae' class, although the two are functionally equivalent for I showed that the S. cerevisiae DPM1 gene and its human counterpart both complement the lethal dpm1$\sp+$ null mutation in S. pombe. The 'human' class of Dol-P-Man synthases, however, do not complement an S. cerevisiae dpm1 null mutant, and, unlike the S. cerevisiae class of enzymes, do not confer Dol-P-Man synthetic activity on E. coli cells. I propose that the 'human' class of Dol-P-Man synthase requires one or more auxiliary proteins for catalytic activity or to mediate membrane association. The facts that Dol-P-Man synthase is an essential enzyme in yeast, and that the Ustilago and Trypanosoma synthases are in a different class from the human enzyme, raises the possibility that Dol-P-Man synthase could be exploited as a target for selective inhibitors of pathogenic eukaryotic microbes.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Colussi, Paul Attilio

Contributors dc:contributor

• Peter A.B.Orlean

• Biology, Microbiology

Language dc:language

eng

Identifier

(MiAaPQ)AAI9737080

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84881