Structure Determination for Medical Structural Genomics of Pathogenic Protozoa

该项目将确定一组重要真核病原体的关键蛋白质的晶体结构。这将为后续针对相应疾病的生物化学研究和基于结构的药物设计奠定基础。这些疾病包括主要的世界性疾病（疟疾、昏睡病、南美锥虫病）和与生物防御有关的感染。该项目是涉及华盛顿大学多个小组合作的一个组成部分，共同包括从靶基因组中鉴定相关蛋白质序列，从这些靶点表达的蛋白质的表达和结晶，以及鉴定可能开发为药物设计先导化合物的配体。将结合SGPP内部开发的用于结构测定的高通量技术 随着大规模化学建模和生化筛选的输出，以生成关键蛋白质和蛋白质：配体复合物的三维结构。

This Project will determine crystal structures of key proteins from a set of important eukaryotic pathogens. It will lay groundwork for subsequent biochemical studies and structure-based drug design targeting the corresponding diseases. These diseases include both major world scourges (malaria, sleeping sickness, Chagas' disease) and infections relevant to biodefense. The project is one component of collaboration involving multiple groups at the University of Washington, which jointly encompass the identification of relevant protein sequences from the target genomes, the expression and crystallization of protein expressed from these targets, and the identification of ligands that may be developed into lead compounds for drug design. The high-throughput technology developed within SGPP for structure determination will be combined with the output of large-scale chemical modeling and biochemical screening to generate three-dimensional structures for key proteins and protein:ligand complexes.