Yakusheva M I, Poznanskaya A A, Pospelova T A, Rudakova I P, Yurkevich A M, Yakovlev V A
Biochim Biophys Acta. 1977 Sep 15;484(1):216-35. doi: 10.1016/0005-2744(77)90127-9.
A new method of partial chemical synthesis of adenosylcobalamin (Co alpha-[alpha-5,6-diemethylbenzimidazolyl)]-Co beta-adenosylcobamide, AdoCbl) analogs has been developed. A series of derivatives of AdoCbl modified in the nucleoside and nucleotide ligands and corrin macrocycle have been obtained. The interaction of AdoCl analogs with glycerol dehydratase (EC 4.2.1.30) from Aerobacter aerogenes has been investigated. It has been shown that the nucleoside ligand of AdoCbl provides no essential contribution to the binding of apoenzyme but the preservation of the exact structure of the 1-N and 2-C positions of adenine appears essential for the catalysis. The coordination bond between the Co and nucleotide ligand of AdoCl does not play a decisive role in glycerol dehydratase activity. To form the active site of the glycerol dehydrates, the nucleotide in the AdoCbl structure is essential since nucleotide elimination results in a 100-fold increase of Ki for the corresponding analog. In the binding of AdoCbl with apoenzyme, the main role belongs to the corrin macrocycle, in which the e-propionamide group is significant for binding with apoenzyme, but presumably not essential for catalysis.
已开发出一种腺苷钴胺素（辅酶α-[α-5,6-二甲基苯并咪唑基)]-辅酶β-腺苷钴胺酰胺，AdoCbl）类似物的部分化学合成新方法。已获得一系列在核苷和核苷酸配体以及咕啉大环中修饰的AdoCbl衍生物。研究了AdoCbl类似物与产气气杆菌甘油脱水酶（EC 4.2.1.30）的相互作用。结果表明，AdoCbl的核苷配体对脱辅基酶的结合没有重要贡献，但腺嘌呤1-N和2-C位置精确结构的保留对催化似乎至关重要。AdoCbl的Co与核苷酸配体之间的配位键在甘油脱水酶活性中不起决定性作用。为了形成甘油脱水酶的活性位点，AdoCbl结构中的核苷酸至关重要，因为去除核苷酸会导致相应类似物的Ki增加100倍。在AdoCbl与脱辅基酶的结合中，主要作用属于咕啉大环，其中ε-丙酰胺基团对于与脱辅基酶的结合很重要，但可能对催化不是必需的。
