We are characterizing the Estrogen Binding Protein (EBP1) isolated from the pathogenic fungus C. albicans, in order to identify the physiological role of this enzyme. Various lines of evidence suggest a relationship between estrogens and the pathogenicity of this organism, and this protein represents the only estrogen binding activity identified in C. albicans. Therefore, we are pursuing the hypothesis that this protein is involved in potentiating virulence. Recent work has demonstrated that EBP1 is homologous to an enzyme found in plants involved in a lipid signaling pathway, and we are attempting to show that EBP1 has a similar function in C. albicans. Our approach in solving this problem has been to study the structure of a highly conserved homolog using the Computer Graphics Lab resources in order to identify and generate active site mutants that are fully competent in substrate binding, but catalytically compromised. These mutant proteins will then be used to trap the biological substrate of this protein. One such mutant has been made, and we are currently in the prcess of characterizing its properties. The use of the Computer Graphics Laboratory has been critical in interpreting the data obtained in our laboratory. We believe that this research will enable us to describe an as yet unknown lipid signaling pathway in this fungus, and further understand how the pathogen interacts with its human host.
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