title: Cloning and sequence analysis of a rapamycin-binding protein-encoding gene (RBP1) from Candida albicans.
abstract: 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.
authors.affiliation: Department of Gene Expression Sciences, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406.
authors.forename: A
authors.initials: A
authors.lastname: Ferrara
authors.forename: R
authors.initials: R
authors.lastname: Cafferkey
authors.forename: G P
authors.initials: GP
authors.lastname: Livi
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D002352:Carrier Proteins; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D011090:Polyenes; D022021:Tacrolimus Binding Proteins; D020123:Sirolimus