XAS STUDIES ON HEME PROTEINS

血红素蛋白的 XAS 研究

• 批准号: 8362228
• 负责人: PETER A LAY
• 金额: $ 0.33万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362228
• 关键词: Binding; Brain; Cardiovascular Diseases; Cardiovascular system; Cells; Cerebral Ischemia; Data; Funding; Grant; Health; Heme; Heme Group; Hemeproteins; Human; Hypertension; Kidney; Ligands; Myoglobin; National Center for Research Resources; Nature; Neurodegenerative Disorders; Neurons; Principal Investigator; Procedures; Proteins; Radiation; Research; Research Infrastructure; Resources; Role; Source; Spectrum Analysis; Stroke; Structure; Subcellular structure; Techniques; Tryptophan; Tryptophan 2,3 Dioxygenase; United States National Institutes of Health; absorption; adduct; blood pressure regulation; cost; in vivo; neuroglobin; oxidation; structural biology

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. 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.

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。 血红素蛋白已通过X射线吸收光谱进行了广泛的研究，但是新的蛋白质/角色继续出现。 XANE和多片XAFS研究是其氧化状态，配位数和配位配体的性质的敏感探针。我们将研究血红素结构在脑部疾病中神经蛋白（NB）在大脑中的作用，肌红蛋白（MB）的其他功能，以及新的蛋白质，吲哚胺2,3-二氧酶-2（IDO-2）。我们将使用这些技术比较分离的蛋白质的不同加合物和氧化态的结构与细胞中包含的蛋白质的结构。特别是，NB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情况下神经元和中风和神经退行性疾病的神经元中细胞内神经蛋白结构的变化。同样，在心血管系统的健康中没有与MB的结合很重要，但是尚不确定它是否与硫醇酸盐组，血红素中心或体内人体MB结合。我们将比较来自分离的蛋白质的XAS数据与在与正常情况以及与心血管疾病相关的各种条件下发现的细胞中发现的XAS数据。最后，最近发现的IDO-2代谢了色氨酸，就像研究精通的IDO（现在称为IDO-1）一样。但是，与IDO-1不同，IDO-2在分离和纯化蛋白质时会失去其活性。 XAS将用于研究隔离程序期间发生的结构变化，以确定体内可能的活动结构。这很重要，因为有越来越多的证据表明，肾脏中的IDO-2在控制血压中起着作用，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具有许多潜在的应用在低血压和高血压的治疗中。