Cloning and sequence analysis of a rapamycin-binding protein-encoding gene (RBP1) from Candida albicans.
Rapamycin (Rm) and FK506 are macrolide antifungal agents that exhibit potent immunosuppressive properties in higher eukaryotes which are mediated through interaction with specific receptor proteins (FKBPs or RBPs, for FK506- and Rm-binding proteins, respectively). These proteins possess peptidyl-prolyl cis-trans isomerase (PPIase) activity in vitro which is inhibited by the binding of Rm and FK506. We previously isolated a gene encoding an RBP from Saccharomyces cerevisiae, and demonstrated that null mutations in this gene (called RBP1) result in a recessive Rm-resistant (RmR) phenotype. We now have cloned the Candida albicans RBP1 gene via complementation of the RmR phenotype in S. cerevisiae. The predicted C. albicans RBP exhibits 61%, 52% and 49% amino acid (aa) sequence identity with RBPs (FKBPs) from S. cerevisiae, Neurospora crassa and human cells (FKBP-12), respectively. Furthermore, several of the aa residues identified as being important for drug binding in human FKBP-12 are conserved within the C. albicans RBP.
Ferrara
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Department of Gene Expression Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
Cafferkey
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Livi
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D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000378:metabolism*; D001483:Base Sequence; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics*; D003001:Cloning, Molecular / Q000379:methods; D005656:Fungal Proteins / Q000235:genetics*; D015723:Gene Library; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D006360:Heat-Shock Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011090:Polyenes / Q000378:metabolism*; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D020123:Sirolimus; D022021:Tacrolimus Binding Proteins
D000935:Antifungal Agents; D002352:Carrier Proteins; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D011090:Polyenes; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus