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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 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，这是转硫途径中重要的最后一步，从甲硫氨酸循环中去除硫并将其用于半胱氨酸和谷胱甘肽的生产。由于同型半胱氨酸在心脏病中的作用已知，以及同型半胱氨酸调节改变与阿尔茨海默病和帕金森病患者的疾病状态之间的关系已得到证实，人们对 CBS 产生了很大的兴趣。 CBS 是一种吡哆醛 5′-磷酸依赖性酶，它含有血红素辅助因子。然而，据信血红素不参与酶的催化转换。相反，血红素辅助因子与 CBS 活性速率的变构控制有关。 Banerjee 小组已经表明，血红素辅助因子对 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，活性显着降低。血红素的氧化形式和还原形式均通过蛋白质中的组氨酸和半胱氨酸残基轴向协调。这种观点最近因分离出一种新形式的还原性 CBS 而受到挑战，这种新型还原性 CBS 是通过高 pH 值降低而制成的。