This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Emerging infectious diseases continue to be a major threat to public health. Antibiotic resistant bacteria and rapidly mutating viruses are always driving the search for new antibiotic and antiviral targets. Multi-functional multi-domain polyproteins are an essential and underrepresented class of targets, largely due to a lack of structural and functional characterization of these large proteins. We present preliminary results using the technique of small angle x-ray scattering (SAXS) that demonstrate the feasibility of structural studies on polyproteins. We have used a method of overlapping constructs to verify the structures of polyprotein intermediates from the SARS coronavirus. We have also produced SAXS reconstructions of a non-ribosomal peptide synthetase used by pathogenic bacteria to scavenge iron during an infection. The techniques developed by this research will be applicable to a wide range of viruses and bacteria.
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