PROTEIN CRYSTAL STRUCTURE DETERMINATIONS RELATED TO NITRIC OXIDE SIGNALING AND O

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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. We request beam time to further several projects. First, we are studying nitrosylated heme proteins, including nitrophorins and heme-based NO signaling proteins, particularly soluble guanylate cyclase (sGC). Second, we are continuing studies of protein S-nitrosation, and control of glutathione S-nitrosation by the protein GSNO reductase. The GSNOR studies include a drug discovery component. Third, we are investigating proteins involved in riboflavin synthesis, particularly the GTP cyclohydrolases. Fourth, we are expanding studies of proteins involved in metal transport and homeostasis in bacteria, focusing on cusF, silF, cusB, and cueO. Finally, we will, in collaboration with Matt Cordes, use structure determinations guided by transitive homology studies to map fold evolution of Cro proteins and lipocalins. Crystals are available for all projects. Some diffract to 1.0 ¿ or better. Synchrotron radiation is needed for (1) MAD structure determination, (2) to provide sufficient resolution to determine accurate geometrical parameters such as heme distortion from planarity and metal binding site geometries; (3) to provide variable wavelength x-rays for unambiguous identification of bound metal atoms and to control photoreduction of metal sites and S-NO bonds.