HYDROLYSIS OF HEMOGLOBIN BY SCHISTSOMA MANSONI CATHEPSIN B-LIKE CYSTEINEPROTEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在该项目的初步分析中，纯化的重组血吸虫组织蛋白酶B与血红蛋白孵育，并鉴定了血红蛋白降解的片段。最初的裂解似乎是在已知的被其他血红蛋白降解酶裂解的血红蛋白链的“薄弱环节”。随后的降解速度很快，只产生了很小的多肽片段。这项研究证实了血吸虫组织蛋白酶B作为一种“血红蛋白酶”的功效。目前的努力旨在验证血红蛋白和其他宿主血清蛋白作为血吸虫消化蛋白的底物在更“体内”的环境中。随着小鼠感染模型的发展，血吸虫肠道内容物正在被分离和分析，以寻找特定的蛋白质片段。我们正计划确定哪些底物被切割，以及切割的位置，这样我们就可以利用这些信息来识别血吸虫肠道中可能导致特定切割片段的可能的蛋白水解酶。

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.