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.

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