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; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 胱磷脂ββ-合成酶（CBS）催化同型半胱氨酸和丝氨酸的凝结形成胱胱氨而在过硫化途径中的重要最后一步，从甲硫氨酸循环中清除了硫，并将其承诺将其降低至胱天蛋白的产生。由于同型半胱氨酸在心脏病中的已知作用，以及同型半胱氨酸调控与阿尔茨海默氏症患者的疾病状况改变之间的关系，人们对CBS引起了极大的兴趣。 CBS是吡啶还毒5？ - 磷酸依赖性酶，它含有血红素辅因子。然而，血红素不被认为与酶的催化更新有关。相反，血红素辅因子与CBS活性率的变构控制有关。 Banerjee组表明，与Fe（III）形式相比，Fe（II）形式对氧化还原介导的CBS进行了调节，其中Fe（II）形式的活性明显降低。血红素的氧化和还原形式均由组氨酸和来自蛋白质的半胱氨酸残基轴向配位。最近，通过高pH降低制造的一种新形式的减少CBS的新形式对这种观点进行了挑战。