The Journal of Membrane Biology ( IF 2.3 ) Pub Date : 2020-11-18 , DOI: 10.1007/s00232-020-00152-z Ana-Nicoleta Bondar 1
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Transmembrane substrate cleavage by the small Escherichia coli rhomboid protease GlpG informs on mechanisms by which lipid interactions shape reaction coordinates of membrane-embedded enzymes. Here, I review and discuss new work on the molecular picture of protein–lipid interactions that might govern the formation of the substrate–enzyme complex in fluid lipid membranes. Negatively charged PG-type lipids are of particular interest, because they are a major component of bacterial membranes. Atomistic computer simulations indicate POPG and DOPG lipids bridge remote parts of GlpG and might pre-occupy the substrate-docking site. Inhibition of catalytic activity by PG lipids could arise from ligand-like lipid binding at the active site, which could delay or prevent substrate docking. Dynamic protein–lipid H-bond networks, water access to the active site, and fluctuations in the orientation of GlpG suggest that GlpG has lipid-coupled dynamics that could shape the energy landscape of transmembrane substrate docking.
Graphic Abstract
中文翻译：
膜内蛋白酶活性位点处的磷脂酰甘油脂质结合
小大肠杆菌对跨膜底物的裂解菱形蛋白酶 GlpG 告知脂质相互作用形成膜嵌入酶的反应坐标的机制。在这里，我回顾并讨论了关于蛋白质-脂质相互作用的分子图的新工作，这些相互作用可能控制着流体脂质膜中底物-酶复合物的形成。带负电荷的 PG 型脂质特别令人感兴趣，因为它们是细菌膜的主要成分。原子计算机模拟表明 POPG 和 DOPG 脂质桥接 GlpG 的远程部分，并可能预先占据基板对接位置。PG 脂质对催化活性的抑制可能源于活性位点处的配体样脂质结合，这可能会延迟或阻止底物对接。动态蛋白质-脂质 H 键网络，水进入活性位点，
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