STRUCTURAL BASIS FOR SIGNAL TRANSDUCTION BY HEMOPROTEIN SENSORS

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 我们的研究重点是了解气体信使，如NO，CO和O2通过血红素蛋白传感器的信号。 我们已经开始解决这个问题，通过解决关键的血红素蛋白质的晶体结构，要么生物合成信使或得到激活。第一个项目是与我们发现的一种新的祖先一氧化氮合酶（NOS）在细菌中，这像真核酶是二聚体，但缺乏锌结合域。 此外，它们不利用四氢生物蝶呤作为辅因子。 第二个项目涉及可溶性鸟苷酸环化酶（sGC）的结构，其结合NO并催化GTP转化为cGMP。 确定NOS中的电子传递途径和确定NOS-抑制剂相互作用的结构决定因素是第三个项目的基础。 NOS-辅因子相互作用的结构特征也很有趣。 我们的工作重点是阐明NOS结合位点的化学反应性和基于形状的分子识别。 第四个项目涉及确定氧如何结合到一个域介导的趋氧性通过在另一个域的结构变化的分子基础。 bNOS、sGC和航空换能器的结构尚不清楚。

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. The focus of our research is to understand how gaseous messengers such as NO, CO, and O2 transduce signals via hemoprotein sensors. We have begun to address this by solving crystal structures of key heme-containing proteins that either biosynthesize the messenger or get activated by it. The first project is related to our discovery of a novel ancestral nitric oxide synthases (NOS) in bacteria, which like the eukaryotic enzymes are dimeric, but lack the Zn-binding domain. In addition, they do not utilize tetrahydrobiopterin as a cofactor. The second project concerns the structure of soluble guanylyl cyclase (sGC), which binds NO and catalyzes the conversion of GTP to cGMP. Identification of the electron-transfer pathway in NOS and determination of the structural determinants of NOS-inhibitor interactions form the basis of the third project. The structural features of NOS-cofactor interactions are also of interest. We have focused our efforts on elucidating the chemical reactivity and shape-based molecular recognition at work in NOS binding sites. The fourth project deals with identifying the molecular basis of how oxygen binding to one domain mediates aerotaxis via structural changes at another domain. Structures of bNOS, sGC, and the aerotransducer are unknown.