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: 8363752
• 负责人: James H. McKerrow
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8363752
• 关键词: Cathepsins B; Cleaved cell; Development; Funding; Grant; Hemoglobin; Hydrolysis; Incubated; Infection; Link; Mass Spectrum Analysis; National Center for Research Resources; Peptide Fragments; Peptide Hydrolases; Principal Investigator; Protein Fragment; Recombinants; Research; Research Infrastructure; Resources; Schistosoma; Serum Proteins; Site; Source; United States National Institutes of Health; cost; in vivo; mouse model

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. 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 在对该项目的初步分析中，将纯化的重组黑组蛋白酶B与血红蛋白一起孵育，并鉴定出血红蛋白降解的片段。 最初的切割似乎是在其他血红蛋白脱落蛋白酶裂解的血红蛋白链的“弱连接”中。随后的降解很快，仅产生小肽片段。这项研究证实了血吸虫组织B作为“血红蛋白酶”的功效。当前的努力旨在验证血红蛋白和其他宿主蛋白作为在更“体内”环境中的螺杆菌消化蛋白的底物。在小鼠感染模型中发育后反流的血吸虫胆量的含量正在分离并分析特定蛋白质片段。我们正计划确定哪些底物是裂解的，以及乳沟的位点，以便我们可以使用这些信息来识别可能负责特定切割片段的螺纹肠肠的推定蛋白酶。