College of Inter-Faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, Warsaw, Poland.
Centre of New Technologies, University of Warsaw, Warsaw, Poland.
PLoS Comput Biol. 2020 May 26;16(5):e1007904. doi: 10.1371/journal.pcbi.1007904. eCollection 2020 May.
S-adenosylmethionine (SAM) is one of the most important enzyme substrates. It is vital for the function of various proteins, including large group of methyltransferases (MTs). Intriguingly, some bacterial and eukaryotic MTs, while catalysing the same reaction, possess significantly different topologies, with the former being a knotted one. Here, we conducted a comprehensive analysis of SAM conformational space and factors that affect its vastness. We investigated SAM in two forms: free in water (via NMR studies and explicit solvent simulations) and bound to proteins (based on all data available in the PDB and on all-atom molecular dynamics simulations in water). We identified structural descriptors-angles which show the major differences in SAM conformation between unknotted and knotted methyltransferases. Moreover, we report that this is caused mainly by a characteristic for knotted MTs compact binding site formed by the knot and the presence of adenine-binding loop. Additionally, we elucidate conformational restrictions imposed on SAM molecules by other protein groups in comparison to conformational space in water.
S-腺苷甲硫氨酸（SAM）是最重要的酶底物之一。它对各种蛋白质的功能至关重要，包括一大类甲基转移酶（MTs）。有趣的是，一些细菌和真核 MTs 虽然催化相同的反应，但具有明显不同的拓扑结构，前者是一个纽结结构。在这里，我们对 SAM 的构象空间和影响其广泛性的因素进行了全面分析。我们研究了两种形式的 SAM：游离于水中（通过 NMR 研究和显式溶剂模拟）和结合于蛋白质（基于 PDB 中所有可用的数据和在水中进行的全原子分子动力学模拟）。我们确定了结构描述符——角度，这些角度显示了无纽结和纽结甲基转移酶之间 SAM 构象的主要差异。此外，我们报告说，这主要是由于纽结 MTs 紧凑的结合位点由纽结和腺嘌呤结合环形成所致。此外，我们阐明了与水中构象空间相比，其他蛋白质组对 SAM 分子施加的构象限制。
