Centre of Excellence in Biocrystallography, Department of Chemical Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy.
Molecules. 2010 Apr 30;15(5):3228-59. doi: 10.3390/molecules15053228.
The chemistry and biochemistry of the vitamin B(12) compounds (cobalamins, XCbl) are described, with particular emphasis on their structural aspects and their relationships with properties and function. A brief history of B(12), reveals how much the effort of chemists, biochemists and crystallographers have contributed in the past to understand the basic properties of this very complex vitamin. The properties of the two cobalamins, the two important B(12) cofactors Ado- and MeCbl are described, with particular emphasis on how the Co-C bond cleavage is involved in the enzymatic mechanisms. The main structural features of cobalamins are described, with particular reference to the axial fragment. The structure/property relationships in cobalamins are summarized. The recent studies on base-off/base-on equilibrium are emphasized for their relevance to the mode of binding of the cofactor to the protein scaffold. The absorption, transport and cellular uptake of cobalamins and the structure of the B(12) transport proteins, IF and TC, in mammals are reviewed. The B(12) transport in bacteria and the structure of the so far determined proteins are briefly described. The currently accepted mechanisms for the catalytic cycles of the AdoCbl and MeCbl enzymes are reported. The structure and function of B(12) enzymes, particularly the important mammalian enzymes methyltransferase (MetH) and methyl-malonyl-coenzyme A mutase (MMCM), are described and briefly discussed. Since fast proliferating cells require higher amount of vitamin B(12) than that required by normal cells, the study of B(12 )conjugates as targeting agents has recently gained importance. Bioconjugates have been studied as potential agents for delivering radioisotopes and NMR probes or as various cytotoxic agents towards cancer cells in humans and the most recent studies are described. Specifically, functionalized bioconjugates are used as "Trojan horses" to carry into the cell the appropriate antitumour or diagnostic label. Possible future developments of B(12) work are summarized.
本文描述了维生素 B(12) 化合物（钴胺素，XCbl）的化学和生物化学性质，特别强调了它们的结构方面及其与性质和功能的关系。B(12) 的简要历史揭示了化学家和生物化学家以及晶体学家过去为理解这种非常复杂的维生素的基本性质做出了多少贡献。本文描述了两种钴胺素，两种重要的 B(12) 辅酶 Ado-和 MeCbl 的性质，特别强调了 Co-C 键的断裂如何参与酶促机制。描述了钴胺素的主要结构特征，特别参考了轴向片段。总结了钴胺素的结构-性质关系。强调了碱基离基-碱基结合平衡的最新研究，因为它们与辅因子与蛋白质支架结合的模式有关。综述了哺乳动物中钴胺素的吸收、转运和细胞摄取以及 B(12) 转运蛋白 IF 和 TC 的结构。简要描述了细菌中的 B(12) 转运和迄今确定的蛋白质的结构。报告了 AdoCbl 和 MeCbl 酶的催化循环的当前接受机制。描述了 B(12) 酶的结构和功能，特别是重要的哺乳动物酶甲基转移酶（MetH）和甲基丙二酰辅酶 A 变位酶（MMCM），并进行了简要讨论。由于快速增殖的细胞比正常细胞需要更高量的维生素 B(12)，因此最近研究了 B(12) 缀合物作为靶向剂。生物缀合物已被研究为向人体中的癌细胞输送放射性同位素和 NMR 探针或作为各种细胞毒性剂的潜在剂，并且描述了最近的研究。具体而言，功能化的生物缀合物被用作“特洛伊木马”，将适当的抗肿瘤或诊断标签带入细胞。总结了 B(12) 工作的可能未来发展。
