MEDICAL STRUCTURAL GENOMICS OF PATHOGENIC PROTOZOA

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该建议构成了华盛顿大学几个研究小组（PI Ethan Merritt，Dustin Maly，Fred Buckner，Wesley货车Voorhis，Erkang Fan，Christophe Verlinde，Wim Hol）合作的晶体学组成部分。获得SSRL光束线将使我们能够确定一组重要的真核病原体的关键蛋白质和蛋白质：配体复合物的晶体结构。前4年的研究为后续针对相应疾病的生化研究和基于结构的药物设计奠定了基础。这些疾病包括世界主要疾病（疟疾、昏睡病、南美锥虫病？疾病）和其他对第三世界健康造成不成比例影响的感染。晶体学将与化学建模和生化筛选的输出相结合，以进行配体发现，识别潜在的药物先导，并为候选药物的开发提供SAR。

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. This proposal constitutes the crystallographic component of a collaboration among several research groups at the University of Washington (PIs Ethan Merritt, Dustin Maly, Fred Buckner, Wesley van Voorhis, Erkang Fan, Christophe Verlinde, Wim Hol). Access to SSRL beamlines will allow us to determine crystal structures of key proteins and protein:ligand complexes from a set of important eukaryotic pathogens. The previous 4 years of study has laid the groundwork for subsequent biochemical studies and structure-based drug design targeting the corresponding diseases. These include major world scourges (malaria, sleeping sickness, Chagas? disease) and other infections with a disproportionate impact on Third World health. Crystallography will be combined with the output of chemical modeling and biochemical screening to conduct ligand discovery, to identify potential drug leads, and to provide SAR for the development of candidate drugs.