Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email:
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Annu Rev Biochem. 2018 Jun 20;87:555-584. doi: 10.1146/annurev-biochem-062917-012500.
S-adenosylmethionine (AdoMet) has been referred to as both "a poor man's adenosylcobalamin (AdoCbl)" and "a rich man's AdoCbl," but today, with the ever-increasing number of functions attributed to each cofactor, both appear equally rich and surprising. The recent characterization of an organometallic species in an AdoMet radical enzyme suggests that the line that differentiates them in nature will be constantly challenged. Here, we compare and contrast AdoMet and cobalamin (Cbl) and consider why Cbl-dependent AdoMet radical enzymes require two cofactors that are so similar in their reactivity. We further carry out structural comparisons employing the recently determined crystal structure of oxetanocin-A biosynthetic enzyme OxsB, the first three-dimensional structural data on a Cbl-dependent AdoMet radical enzyme. We find that the structural motifs responsible for housing the AdoMet radical machinery are largely conserved, whereas the motifs responsible for binding additional cofactors are much more varied.
S-腺苷甲硫氨酸（AdoMet）被称为“穷人的腺苷钴胺素（AdoCbl）”和“富人的腺苷钴胺素”，但今天，随着越来越多的功能被归因于每种辅助因子，两者似乎同样丰富和令人惊讶。最近在一种 AdoMet 自由基酶中对有机金属物种的特征描述表明，在自然界中区分它们的界限将不断受到挑战。在这里，我们比较和对比了 AdoMet 和钴胺素（Cbl），并考虑了为什么依赖于 Cbl 的 AdoMet 自由基酶需要两种如此相似的反应性辅助因子。我们进一步进行结构比较，使用最近确定的氧杂环丁烷-A 生物合成酶 OxsB 的晶体结构，这是第一个关于依赖于 Cbl 的 AdoMet 自由基酶的三维结构数据。我们发现，负责容纳 AdoMet 自由基机构的结构基序在很大程度上是保守的，而负责结合其他辅助因子的基序则更加多样化。
