An estrogen binding protein has been isolated from Candida albicans, a normal yeast member of human microbiological flora that causes opportunistic infections in immunocompromised individuals and in otherwise healthy women. Evidence has been presented that estrogens can stimulate conversion of the normal yeast form of Candida to the infectious hyphal form suggesting that levels of circulating estrogens may directly affect the virulence of resident Candida. The estrogen binding protein is a redox-active flavoenzyme, whose function is unknown. Our initial studies have focused on characterizing the in vitro ligand binding and catalytic a ctivities of the enzyme with a goal of using this knowledge to design chemical/biochemical approaches to identify the enzyme's in vivo substrate and function. Along these lines we are interested in generating mutants with altered catalytic and/or ligand binding properties that may be useful in trapping in vivo substrates. At present there is no crystal structure of the enzyme, but we have been able to generate a homology model of the enzyme based on the structure of a highly homologous enzyme from Saccharomyces cerevisiae. In addition, our crystallographer collaborators have found better crystallization conditions, which they are further optimizing. We have recently generated a mutant of the enzyme based on the model, and are in the process of characterizing it.
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