Siderophores are secondary metabolites produced by microorganisms to acquire Fe(III) from the aerobic environment. The ferrisiderophores are transported into the cells by an high affinity uptake system which uses several membrane proteins. Many different siderophores are produced for competitive reasons and therefore a variety of matching uptake systems exist. The present research will concentrate on the discovery of new siderophores primarily from pathogenic species and attempt an explanation of the specificity of siderophores for Fe+++, using normal and high-angle x-ray diffraction and other structural techniques. Structural studies will be performed on orally effective synthetic analogs used against iron overload and the stereochemistry of ferrisiderophores will be explored by theoretical methods, modeling and structure determinations. A large quantity of the purified FepA, E. coli receptor protein for Fe(III) enterobactin will be produced and used to improve the quality of FepA crystals and to prepare crystals of heavy atom derivatives to be used in the structure determination of the protein. A concentrated study will be made on the binding properties and other physical-chemical properties of isolated and purified receptor and transport proteins involved in translocation and uptake of ferrisiderophores in E. coli and several Pseudomonas species as well as fungus. These results will be correlated with kinetic transport studies. The research is planned to understand the competitiveness and pathogenicity of microbes in infection and their antagonism in the environment and, most important, to obtain a molecular understanding of transmembrane iron transport.
| Piyamongkol, Sirivipa; Ma, Yong M; Kong, Xiao L et al. (2010) Amido-3-hydroxypyridin-4-ones as iron(III) ligands. Chemistry 16:6374-81 |
