CAMP RECEPTOR PROTEIN FROM MYCOBACTERIUM TUBERCULOSIS

来自结核分枝杆菌的 CAMP 受体蛋白

基本信息

项目摘要

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. This protein is usually called CRP. This can stand for "cAMP receptor protein" OR catabolite repressor protein". In E. coli the homolog was solved about 20 years ago by Steitz etal, and has become a textbook lesson in gene regulation because it *binds cAMP *then binds DNA at many repressors *shuts off several sugar-utilization pathways *bends the DNA where it binds. The present project is CRP from Mycobacterium tuberculosis. It is 30% identical but Molec Replacement has failed. Why pursue the structure of this homolog? In Mt, the functions are not identical; there are more genetic effects than in Ecoli. Also, Mt is an important pathogen target. Also, the previous work in Ecoli has failed to give a structure of the unliganded protein. We have crystallized the unliganded form, along with liganded forms. We have crystallized the protein in three forms: unliganded, with cAMP, and with cAMP and DNA. We hope to see the structure in all 3 forms and assess conformational changes. This will advance the fields of transcription and gene regulation in structural biology, and also provide data on tuberculosis pathogens.
这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者(PI)可能从另一个NIH来源获得了主要资金, 因此可以在其他CRISP条目中表示。所列机构为 研究中心,而研究中心不一定是研究者所在的机构。 这种蛋白质通常被称为CRP。 这可以代表“cAMP受体蛋白”或“分解代谢物阻遏蛋白”。在大肠大约20年前,Steitz埃塔尔解决了大肠杆菌的同源物,并已成为基因调控的教科书,因为它 * 结合cAMP * 然后在许多阻遏物处结合DNA * 关闭几种糖利用途径 * 在DNA结合的地方弯曲。 本项目是来自结核分枝杆菌的CRP。它是30%相同的,但Molec更换失败。为什么要研究这个同系物的结构?在Mt中,功能并不相同;比大肠杆菌有更多的遗传效应。 此外,MT是一个重要的 病原体靶标 此外,之前在大肠杆菌中的工作未能给出无配体蛋白质的结构。我们已经结晶了无配体的形式,沿着有配体的形式。 我们已经将蛋白质结晶为三种形式:未配体的、有cAMP的、有cAMP和DNA的。 我们希望看到所有3种形式的结构并评估构象变化。这将推进结构生物学中的转录和基因调控领域,并提供有关结核病病原体的数据。

项目成果

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