STRUCTURAL STUDIES ON COBALAMIN COMPLEXES

钴胺素复合物的结构研究

• 批准号: 8362078
• 负责人: CLYDE A SMITH
• 金额: $ 0.06万
• 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/8362078
• 关键词: Animals; Biological; Blood; Cells; Clinical; Cobalamin; Complex; Corrinoids; Enzymes; Food; Funding; Grant; Human; Mammalian Cell; Megaloblastic Anemia; Metabolism; National Center for Research Resources; Nature; Neuropathy; Pernicious Anemia; Play; Principal Investigator; Radiation; Reporting; Research; Research Infrastructure; Resources; Sampling; Seaweed; Source; Structure; Tissues; United States National Institutes of Health; aquacobalamin; cobamamide; cost; glutathionylcobalamin; microbial; nitritocobalamin; nitrosocobalamin; structural biology; sulfitocobalamin

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. Corrinoid-dependent enzymes are widespread in nature and play key roles in human, animal and microbial metabolism. The clinical hallmarks of B12 deficiency are megaloblastic anemia (?pernicious anemia?), and neuropathies. Upon reaching cells, cobalamin derivatives are converted to MeCbl and AdoCbl by currently ill-defined mechanisms. Many studies have been carried out over the past several decades involving the extraction and identification of cobalamins from mammalian cells, tissue and blood, in addition to other biological samples such as foods and seaweed. Adenosylcobalamin, methylcobalamin and aquacobalamin are the major cobalamin metabolites isolated from biological samples but there are also reports of the isolation of nitrocobalamin and sulfitocobalamin from biological sources, along with other unknown complexes. We have synthesized a number of cobalamin derivatives to assist in the identification of unknown cobalamins isolated from biological samples, and we have determined the crystal structures of a number of these complexes, including N-acetylcysteinylcobalamin and nitrosocobalamin. The structures of two alkylcobalamins, ethylcobalamin and butylcobalamin have also been determined and recently reported. Further studies on other biologically-relevent cobalamin complexes are underway, including glutathionylcobalamin which has for many years evaded all attempts at structure determination.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 类固醇依赖的酶在自然界中广泛存在，在人类、动物和微生物代谢中发挥着关键作用。B12缺乏的临床特征是巨幼细胞性贫血(恶性贫血)和神经病变。在到达细胞后，钴胺衍生物通过目前定义不清的机制转化为MeCbl和Adobe Cbl。在过去的几十年里，除了食物和海藻等其他生物样本外，还进行了许多研究，涉及从哺乳动物细胞、组织和血液中提取和鉴定钴蛋白。腺苷钴胺、甲钴胺和水钴胺是从生物样品中分离得到的主要钴胺代谢物，但也有报道从生物来源中分离出硝酸钴胺和硫钴胺，以及其他未知的络合物。我们合成了一些钴胺类化合物来辅助从生物样品中分离出未知的钴胺类化合物，并测定了其中一些配合物的晶体结构，包括N-乙酰半胱氨酸钴胺和亚硝酸钴胺。乙基钴胺和丁基钴胺两种烷基钴胺的结构也得到了测定和最近的报道。对其他与生物相关的钴胺络合物的进一步研究正在进行中，包括谷胱甘肽钴胺，它多年来一直逃避所有结构测定的尝试。