作为细胞过程的终极中介物的很多小分子仍未得到描述和报告，因为它们的身份通过以代谢通道为目标的传统方法可能无法确定。
JungwookKim等人识别出了这样一个分子，即carboxy-S-adenosyl-L-methionine(Cx-SAM)。这个人们以前不知道的代谢物是在对大肠杆菌的CmoA酶（SAM-依赖性甲基转移酶超级家族的一个成员）所进行的一项结构研究中发现的。Cx-SAM被埋在CmoA的活性点中。本文作者确定了Cx-SAM的生物合成通道（其合成是通过一个异常活泼的“叶立德中间体”进行的），并且发现，该代谢物在一系列细菌的tRNA修饰中起一定作用。这项研究凸显了结构基因组研究对于发现新颖代谢物和通道的潜力。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature doi:10.1038/nature12180
Structure-guided discovery of the metabolite carboxy-SAM that modulates tRNA function
Jungwook Kim,Hui Xiao,Jeffrey B. Bonanno, Chakrapani Kalyanaraman,Shoshana Brown, Xiangying Tang, Nawar F. Al-Obaidi, Yury Patsko
The identification of novel metabolites and the characterization of their biological functions are major challenges in biology. X-ray crystallography can reveal unanticipated ligands that persist through purification and crystallization. These adventitious protein–ligand complexes provide insights into new activities, pathways and regulatory mechanisms. We describe a new metabolite, carboxy-S-adenosyl-L-methionine (Cx-SAM), its biosynthetic pathway and its role in transfer RNA modification. The structure of CmoA, a member of the SAM-dependent methyltransferase superfamily, revealed a ligand consistent with Cx-SAM in the catalytic site. Mechanistic analyses showed an unprecedented role for prephenate as the carboxyl donor and the involvement of a unique ylide intermediate as the carboxyl acceptor in the CmoA-mediated conversion of SAM to Cx-SAM. A second member of the SAM-dependent methyltransferase superfamily, CmoB, recognizes Cx-SAM and acts as a carboxymethyltransferase to convert 5-hydroxyuridine into 5-oxyacetyl uridine at the wobble position of multiple tRNAs in Gram-negative bacteria, resulting in expanded codon-recognition properties. CmoA and CmoB represent the first documented synthase and transferase for Cx-SAM. These findings reveal new functional diversity in the SAM-dependent methyltransferase superfamily and expand the metabolic and biological contributions of SAM-based biochemistry. These discoveries highlight the value of structural genomics approaches in identifying ligands within the context of their physiologically relevant macromolecular binding partners, and in revealing their functions.
