STRUCTURAL STUDIES ON COBALAMIN COMPLEXES

钴胺素复合物的结构研究

• 批准号: 8169968
• 负责人: CLYDE A SMITH
• 金额: $ 0.27万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169968
• 关键词: Animals; Biological; Blood; Cells; Clinical; Cobalamin; Complex; Computer Retrieval of Information on Scientific Projects Database; Corrinoids; Enzymes; Food; Funding; Grant; Human; Institution; Mammalian Cell; Megaloblastic Anemia; Metabolism; Nature; Neuropathy; Pernicious Anemia; Play; Reporting; Research; Research Personnel; Resources; Role; Sampling; Seaweed; Source; Structure; Tissues; United States National Institutes of Health; aquacobalamin; cobamamide; glutathionylcobalamin; microbial; nitritocobalamin; nitrosocobalamin; sulfitocobalamin

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. 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.

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。子项目和 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。 类咕啉依赖性酶在自然界中广泛存在，在人类、动物和微生物的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。到达细胞后，钴胺素衍生物通过目前尚不明确的机制转化为 MeCbl 和 AdoCbl。过去几十年来，人们进行了许多研究，涉及从哺乳动物细胞、组织和血液以及食物和海藻等其他生物样品中提取和鉴定钴胺素。腺苷钴胺、甲基钴胺和水钴胺是从生物样品中分离的主要钴胺素代谢物，但也有报道从生物来源中分离硝基钴胺和硫钴胺以及其他未知复合物。 我们合成了许多钴胺素衍生物，以协助鉴定从生物样品中分离出的未知钴胺素，并且我们已经确定了许多此类复合物的晶体结构，包括 N-乙酰半胱氨酰钴胺素和亚硝基钴胺素。 两种烷基钴胺素、乙基钴胺素和丁基钴胺素的结构也已被确定并最近被报道。 对其他生物学相关的钴胺素复合物的进一步研究正在进行中，其中包括谷胱甘肽钴胺素，它多年来一直回避所有结构测定的尝试。