SOLUTION SCATTERING IN THE STUDY OF POLYPROTEIN STRUCTURE IN INFECTIOUS DISEASES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 新出现的传染病仍然是对公众健康的主要威胁。抗生素耐药性细菌和快速变异的病毒一直在推动寻找新的抗生素和抗病毒靶标。多功能多结构域多蛋白是一类重要且代表性较低的靶蛋白，这主要是由于缺乏对这些大蛋白的结构和功能表征。我们给出了利用小角X射线散射(SAXS)技术的初步结果，证明了研究多蛋白结构的可行性。我们使用重叠构建的方法来验证SARS冠状病毒多蛋白中间体的结构。我们还制作了一种非核糖体多肽合成酶的SAXS重建，该酶被病原菌用来在感染期间清除铁。这项研究开发的技术将适用于广泛的病毒和细菌。

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. Emerging infectious diseases continue to be a major threat to public health. Antibiotic resistant bacteria and rapidly mutating viruses are always driving the search for new antibiotic and antiviral targets. Multi-functional multi-domain polyproteins are an essential and underrepresented class of targets, largely due to a lack of structural and functional characterization of these large proteins. We present preliminary results using the technique of small angle x-ray scattering (SAXS) that demonstrate the feasibility of structural studies on polyproteins. We have used a method of overlapping constructs to verify the structures of polyprotein intermediates from the SARS coronavirus. We have also produced SAXS reconstructions of a non-ribosomal peptide synthetase used by pathogenic bacteria to scavenge iron during an infection. The techniques developed by this research will be applicable to a wide range of viruses and bacteria.