Inositol phosphoryl transferases from human pathogenic fungi.
The IPC1 gene from Saccharomyces cerevisiae, which encodes inositolphosphorylceramide (IPC) synthase, was first identified as a novel and essential gene encoding resistance to the natural product antifungal aureobasidin A (AUR1). The formation of IPC in fungi is essential for viability, suggesting inhibitors of IPC1p function would make ideal antifungal drug candidates. Homologs of the AUR1/IPC1 gene were identified from a number of human pathogenic fungi, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis and Cryptococcus neoformans. Comparison of these genes with other homologous genes from Candida albicans, Aspergillus fumigatus, Aspergillus nidulans, Saccharomyces cerevisiae and Schizosaccharomyces pombe reveals a conserved structural motif for inositolphosphoryl transferases which is similar to a motif recently described for lipid phosphatases, but with unique characteristics.
Heidler
S A
SA
Department of Infectious Diseases Research, Lilly Research Laboratories, Eli Lilly and Co., Indianapolis, IN 46285, USA.
Radding
J A
JA
D002175:Candida / Q000201:enzymology / Q000235:genetics*; D002384:Catalysis; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics; D003455:Cryptococcus neoformans / Q000201:enzymology / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics*; D006602:Hexosyltransferases / Q000235:genetics*; D008969:Molecular Sequence Data; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D006602:Hexosyltransferases; C088714:phosphatidylinositol-ceramide phosphoinositol transferase; C109311:IPT1 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor)