CRYSTAL STRUCTURES OF VIRULENCE FACTORS, HOST MOLECULES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The SSRL has been a principal resource for x-ray data collection and phasing for my laboratory over the past 5 years. Through the use of MAD phasing at Se, Br, and Zn edges, we have determined many protein structures ab initio. The high brightness, collimation and stability of the monochromatic x-rays has also allowed us to collect high resolution data from crystals with large unit cells which has provided the necessary data for understanding biological function at the atomic level, or for the rational design of small molecule inhibitors for drug design. We propose to continue our work in three areas: studies of the anthrax toxin components, their complexes with small molecule drug leads and host cell target proteins; studies of key structural and signaling molecules involved in integrin-mediated cell migration; and molecules involved in apoptosis, both host cell regulators and their pathogenic subverters (virulence factors).