STRUCTURE DETERMINATION OF KEY PROTEINS IN IMMUNOSUPPRESSIVE PATHWAY

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Abstract

Human dihydroorotate dehydrogenase is the target of two novel immunosuppressants. They bind to this protein at different sites. One agent was approved as an anti-arthritis drug by the FDA last year. The protein is a membrane-bound protein, and it has two different sites for two different substrates, and another site for a cofactor. None of these sites are identical. High quality crystals are available for both normal protein and SetMet incorporated protein, including varieties of complexes. We want to probe the catalytic and inhibition mechanism of this important protein using high resolution crystal structure. The structures of this protein and its complexes will help design drubs against arthritis, which affects one in six American adults. Multiwavelength-Anomalous Diffraction (MAD) method will be used to determine one complex structure. Native and other complex structures can be solved by difference fourier method. Data collection on BioCARS Station 14-BM-D.