STRUCTURAL STUDIES ON COBALAMIN COMPLEXES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 类柯瑞酸依赖性酶广泛存在于自然界中，在人类、动物和微生物的代谢中起着关键作用。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，钴胺素衍生物通过目前不明确的机制转化为MeCbl和MeCbl。在过去几十年中进行了许多研究，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矿。腺苷钴胺素、甲基钴胺素和水钴胺素是从生物样品中分离的主要钴胺素代谢物，但也有报道称从生物来源中分离出硝基钴胺素和硫维生素钴胺素，以及沿着其他未知的复合物。 我们已经合成了一些钴胺素衍生物，以协助识别未知的钴胺素分离的生物样品，我们已经确定了一些这些复合物的晶体结构，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确定和最近的报道。 对其他生物相关钴胺素复合物的进一步研究正在进行中，包括谷胱甘肽钴胺素，它多年来一直逃避结构测定的所有尝试。

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.