XAS STUDIES ON HEME PROTEINS

血红素蛋白的 XAS 研究

• 批准号: 8170188
• 负责人: PETER A LAY
• 金额: $ 0.75万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8170188
• 关键词: Binding; Brain; Cardiovascular Diseases; Cardiovascular system; Cells; Cerebral Ischemia; Computer Retrieval of Information on Scientific Projects Database; Data; Dioxygenases; Funding; Grant; Health; Heme; Heme Group; Hemeproteins; Human; Hypertension; Institution; Kidney; Ligands; Myoglobin; Nature; Neurodegenerative Disorders; Neurons; Procedures; Proteins; Research; Research Personnel; Resources; Role; Source; Spectrum Analysis; Stroke; Structure; Subcellular structure; Techniques; Tryptophan; United States National Institutes of Health; absorption; adduct; blood pressure regulation; in vivo; indoleamine; neuroglobin; oxidation

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. Heme proteins have been studied extensively by x-ray absorption spectroscopy, but new proteins/roles continue to emerge. XANES and multiple-scattering XAFS studies are sensitive probes of their oxidation state, coordination number and the nature of the coordinating ligands. We will study the heme structures with respect to the roles of neuroglobin (Nb) in the brain, NO binding and other functions of myoglobin (Mb) in cardiovascular disease, and the new protein, indoleamine 2,3-dioxygenase-2 (IDO-2), in the kidneys. We will use these techniques to compare the structures of different adducts and oxidation states of the isolated proteins with those contained within cells. In particular, whether Nb confers neuro-protection during cerebral ischemia is controversial and we plan to study changes in the structures of intracellular neuroglobin in neurons under normal conditions and those associated with stroke and neurodegenerative diseases. Similarly, NO binding to Mb is important in the health of the cardiovascular system, but it is uncertain as to whether it binds to the thiolate group, the heme centre or both in human Mb in vivo. We will compare the XAS data from isolated proteins with those found in cells under various conditions associated with normal conditions and those associated with cardiovascular disease. Finally, the recently discovered IDO-2 metabolizes tryptophan, like the well-studied IDO (now known as IDO-1). However, IDO-2, unlike IDO-1, loses its activity when the protein is isolated and purified. XAS will be used to study the structural changes that occur during the isolation procedures in order to ascertain the likely active structure in vivo. This is important as there is mounting evidence that IDO-2 in the kidney has a role in controlling blood pressure and, hence, understanding the nature of the active form and how its activity may be modulated to control blood pressure has many potential applications in the treatment of both low and high blood pressure.

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。 血红素蛋白已经通过X射线吸收光谱进行了广泛的研究，但新的蛋白质/作用不断出现。XANES和多重散射XAFS研究是它们的氧化态，配位数和配位配体的性质的灵敏探针。我们将研究血红素结构与脑红蛋白（Nb）在脑中的作用，心血管疾病中肌红蛋白（Mb）的NO结合和其他功能，以及肾脏中的新蛋白质吲哚胺2，3-双加氧酶-2（IDO-2）。我们将使用这些技术来比较不同的加合物的结构和氧化态的分离的蛋白质与细胞内所包含的。特别是，铌是否赋予脑缺血期间的神经保护是有争议的，我们计划研究在正常条件下的神经元和与中风和神经退行性疾病相关的细胞内神经红蛋白的结构的变化。同样，NO与Mb的结合对于心血管系统的健康很重要，但尚不确定它是否在体内与人Mb中的硫醇基、血红素中心或两者结合。我们将比较来自分离蛋白质的XAS数据与在与正常条件相关的各种条件下的细胞中发现的那些数据以及与心血管疾病相关的那些数据。最后，最近发现的IDO-2代谢色氨酸，就像研究充分的IDO（现在称为IDO-1）一样。然而，与IDO-1不同，IDO-2在分离和纯化蛋白质时失去其活性。XAS将用于研究分离过程中发生的结构变化，以确定体内可能的活性结构。这是重要的，因为有越来越多的证据表明肾脏中的IDO-2在控制血压中起作用，因此，了解活性形式的性质以及如何调节其活性以控制血压在治疗低血压和高血压中具有许多潜在的应用。