Laboratory of Bioinformatics and Systems Biology, Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Warsaw, Poland.
PLoS One. 2011;6(8):e23168. doi: 10.1371/journal.pone.0023168. Epub 2011 Aug 9.
Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity). Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity.
甲基化是生物活性分子中最常见的化学修饰之一，存在于所有生命形式中。其功能作用非常多样化，涉及许多重要的细胞过程，如信号转导、转录调控、生物合成和代谢。在这里，我们通过对其基因组中编码的所有甲基转移酶进行全面的结构和功能调查，进一步了解酿酒酵母中的酶促甲基化。我们使用远缘同源检测和折叠识别，发现酿酒酵母的甲基转移酶组由 86 种 MTases（53 种已知和 33 种具有未知底物特异性的假定 MTases）组成。它们催化结构域的结构分类表明，这些酶可能采用九种不同的折叠，最常见的是罗斯曼样折叠。我们还分析了这些蛋白质的结构域体系结构，并确定了几种新的结构域环境。有趣的是，我们发现大多数 MTase 基因在酵母代谢周期中周期性表达。这一发现，连同计算出的等电点、折叠分配和细胞定位，被用于开发一种预测底物特异性的新方法。使用这种方法，我们预测了 33 种假定 MTase 中的 24 种的一般底物，并在两个经过测试的案例中通过实验证实了这些预测。最后，我们表明，在酿酒酵母中，甲基化由 34 种 RNA MTases、32 种蛋白质 MTases、8 种小分子 MTases、3 种脂质 MTases 和 9 种具有未知底物特异性的 MTases 完成。
