作為細(xì)胞過(guò)程的終極中介物的很多小分子仍未得到描述和報(bào)告,，因?yàn)樗鼈兊纳矸萃ㄟ^(guò)以代謝通道為目標(biāo)的傳統(tǒng)方法可能無(wú)法確定,。
JungwookKim等人識(shí)別出了這樣一個(gè)分子，即carboxy-S-adenosyl-L-methionine(Cx-SAM),。這個(gè)人們以前不知道的代謝物是在對(duì)大腸桿菌的CmoA酶（SAM-依賴性甲基轉(zhuǎn)移酶超級(jí)家族的一個(gè)成員）所進(jìn)行的一項(xiàng)結(jié)構(gòu)研究中發(fā)現(xiàn)的,。Cx-SAM被埋在CmoA的活性點(diǎn)中。本文作者確定了Cx-SAM的生物合成通道（其合成是通過(guò)一個(gè)異?；顫姷?ldquo;葉立德中間體”進(jìn)行的）,，并且發(fā)現(xiàn)，該代謝物在一系列細(xì)菌的tRNA修飾中起一定作用,。這項(xiàng)研究凸顯了結(jié)構(gòu)基因組研究對(duì)于發(fā)現(xiàn)新穎代謝物和通道的潛力,。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
