Institute of Biotechnology, Department of Applied Biochemistry, Technische Universität Berlin, 10623 Berlin, Germany.
Instituto de Recursos Naturales y Agrobiología de Sevilla, Consejo Superior de Investigaciones Científicas, IRNAS-CSIC, 41012 Sevilla, Spain.
Int J Mol Sci. 2022 Dec 2;23(23):15149. doi: 10.3390/ijms232315149.
Analyses of protein structures have shown the existence of molecular channels in enzymes from Prokaryotes. Those molecular channels suggest a critical role of spatial voids in proteins, above all, in those enzymes functioning under high temperature. It is expected that these spaces within the protein structure are required to access the active site and to maximize availability and thermal stability of their substrates and cofactors. Interestingly, numerous substrates and cofactors have been reported to be highly temperature-sensitive biomolecules. Methanogens represent a singular phylogenetic group of Archaea that performs anaerobic respiration producing methane during growth. Methanogens inhabit a variety of environments including the full range of temperatures for the known living forms. Herein, we carry out a dimensional analysis of molecular tunnels in key enzymes of the methanogenic pathway from methanogenic Archaea growing optimally over a broad temperature range. We aim to determine whether the dimensions of the molecular tunnels are critical for those enzymes from thermophiles. Results showed that at increasing growth temperature the dimensions of molecular tunnels in the enzymes methyl-coenzyme M reductase and heterodisulfide reductase become increasingly restrictive and present strict limits at the highest growth temperatures, i.e., for hyperthermophilic methanogens. However, growth at lower temperature allows a wide dimensional range for the molecular spaces in these enzymes. This is in agreement with previous suggestions on a potential major role of molecular tunnels to maintain biomolecule stability and activity of some enzymes in microorganisms growing at high temperatures. These results contribute to better understand archaeal growth at high temperatures. Furthermore, an optimization of the dimensions of molecular tunnels would represent an important adaptation required to maintain the activity of key enzymes of the methanogenic pathway for those methanogens growing optimally at high temperatures.
蛋白质结构分析表明，原核生物的酶中存在分子通道。这些分子通道表明，空间空隙在蛋白质中起着关键作用，尤其是在那些在高温下发挥作用的酶中。预计蛋白质结构内的这些空间是进入活性部位所必需的，并且可以最大限度地提高其底物和辅因子的可用性和热稳定性。有趣的是，已经报道了许多底物和辅因子是高度对温度敏感的生物分子。产甲烷菌代表古菌的一个独特的系统发育群，在生长过程中进行厌氧呼吸产生甲烷。产甲烷菌栖息在多种环境中，包括已知生物形式的全温度范围。在此，我们对在宽温度范围内最佳生长的产甲烷古菌的产甲烷途径中的关键酶的分子隧道进行了维度分析。我们旨在确定分子隧道的尺寸对于那些嗜热酶是否至关重要。结果表明，随着生长温度的升高，甲基辅酶 M 还原酶和异二硫键还原酶中分子隧道的尺寸变得越来越受限，并且在最高生长温度下呈现严格的限制，即对于超嗜热产甲烷菌。然而，在较低温度下生长允许这些酶中的分子空间具有较宽的尺寸范围。这与先前关于分子隧道在维持高温生长的微生物中某些酶的生物分子稳定性和活性方面可能起主要作用的建议一致。这些结果有助于更好地理解高温下的古菌生长。此外，分子隧道尺寸的优化将代表维持在高温下最佳生长的产甲烷途径的关键酶活性所需的重要适应。
