HYDROLYSIS OF HEMOGLOBIN BY SCHISTSOMA MANSONI CATHEPSIN B-LIKE CYSTEINEPROTEASE

曼氏血吸虫组织蛋白酶 B 样半胱氨酸蛋白酶水解血红蛋白

• 批准号: 8169746
• 负责人: James H. McKerrow
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-12 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169746
• 关键词: Cathepsins; Cathepsins B; Cleaved cell; Computer Retrieval of Information on Scientific Projects Database; Development; Funding; Grant; Hemoglobin; Hydrolysis; Incubated; Infection; Institution; Link; Peptide Fragments; Peptide Hydrolases; Protein Fragment; Recombinants; Research; Research Personnel; Resources; Schistosoma; Serum Proteins; Site; Source; United States National Institutes of Health; in vivo; mouse model

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. In the initial analysis for this project, purified recombinant Schistosome cathepsin B was incubated with hemoglobin, and fragments of hemoglobin degradation identified. Initial cleavage appeared to be in a "weak link" of the hemoglobin chain known to be cleaved by other hemoglobin degrading proteases. Subsequent degradation was rapid and yielded only small peptide fragments. This study confirmed the efficacy of the schistosome cathepsin B as a "hemoglobinase". Current efforts are aimed at validating hemoglobin and other host-serum proteins as substrates for schistosome digestive proteases in a more "in vivo" setting. Contents of schistosome guts regurgitated following development in mouse models of infection are being separated and analyzed for specific protein fragments. We are planning to identify both what substrates are cleaved, as well as the sites of cleavage so that we can use this information to identify putative proteases from the schistosome gut that may be responsible for specific cleavage fragments.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在该项目的初步分析中，将纯化的重组血吸虫组织蛋白酶 B 与血红蛋白一起孵育，并鉴定了血红蛋白降解的片段。 最初的切割似乎发生在已知被其他血红蛋白降解蛋白酶切割的血红蛋白链的“薄弱环节”中。随后的降解很快并且仅产生小肽片段。这项研究证实了血吸虫组织蛋白酶 B 作为“血红蛋白酶”的功效。目前的努力旨在在更“体内”的环境中验证血红蛋白和其他宿主血清蛋白作为血吸虫消化蛋白酶的底物。在小鼠感染模型中发育后的血吸虫肠道内容物正在被分离并分析特定的蛋白质片段。我们计划确定哪些底物被切割，以及切割位点，以便我们可以利用这些信息来识别来自血吸虫肠道的可能负责特定切割片段的假定蛋白酶。