STRUCTURAL STUDIES OF THE '424' REDUCED FORM OF CYSTATHIONE B-SYNTHASE

胱硫酮 B 合酶“424”还原形式的结构研究

• 批准号: 7954474
• 负责人: James E. Penner-Hahn
• 金额: $ 0.1万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954474
• 关键词: Commit; Computer Retrieval of Information on Scientific Projects Database; Cystathionine; Cystathionine beta-Synthase; Cysteine; Disease; Enzymes; Funding; Glutathione; Grant; Heart Diseases; Heme; Histidine; Homocysteine; Homocystine; Institution; Mediating; Methionine; Oxidation-Reduction; Parkinson Disease; Pathway interactions; Patients; Physical condensation; Production; Proteins; Pyridoxal Phosphate; Regulation; Research; Research Personnel; Resources; Role; Serine; Source; Sulfur; United States National Institutes of Health; cofactor; heme a; interest; structural biology; synchrotron radiation

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. Cystathionine beta-synthase (CBS) catalyzes the condensation of homocysteine and serine to form cystathionine, the important final step in the transulfuration pathway, removing sulfur from the methionine cycle and committing it to the production of cysteine and glutathione. There has been much interest in CBS due to homocysteine's known role in heart disease, as well as a confirmed relationship between altered homocysteine regulation and disease status for Alzheimers and Parkinsons patients. CBS is a pyridoxal 5?-phosphate dependent enzyme and it contains a heme cofactor. However, the heme is not believed to be involved in the catalytic turnover of the enzyme. Instead the heme cofactor has been implicated in the allosteric control of the rate of activity of CBS. The Banerjee group has shown the regulation of CBS by the heme cofactor to be redox-mediated, where the Fe(II) form shows remarkably decreased activity compared to the Fe(III) form. The oxidized and reduced forms of the heme are both coordinated axially by a histidine and a cysteine residue from the protein. This view was recently challenged with the isolation of a new form of reduced CBS, made by the high pH reduction.

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。 胱硫醚β-合酶（CBS）催化同型半胱氨酸和丝氨酸缩合形成胱硫醚，这是转硫作用途径中重要的最后一步，从甲硫氨酸循环中除去硫并使其产生半胱氨酸和谷胱甘肽。由于同型半胱氨酸在心脏病中的已知作用，以及阿尔茨海默病和帕金森病患者的同型半胱氨酸调节改变与疾病状态之间的关系，CBS引起了很大的兴趣。CBS是吡哆醛5？-磷酸盐依赖性酶，并且其含有血红素辅因子。然而，血红素被认为不参与酶的催化周转。相反，血红素辅因子与CBS活性速率的变构控制有关。Banerjee小组已经表明，通过血红素辅因子对CBS的调节是氧化还原介导的，其中Fe（II）形式与Fe（III）形式相比显示出显著降低的活性。血红素的氧化和还原形式都由来自蛋白质的组氨酸和半胱氨酸残基轴向配位。这一观点最近受到了挑战，分离出一种新形式的还原CBS，由高pH还原制成。