PDF(Pubmed)
Abstract：
Our research aimed to elucidate the mechanism by which aurintricarboxylic acid (ATA) inhibits plasma membrane Ca2+-ATPase (PMCA), a crucial enzyme responsible for calcium transport. Given the pivotal role of PMCA in cellular calcium homeostasis, understanding how it is inhibited by ATA holds significant implications for potentially regulating physiopathological cellular processes in which this pump is involved. Our experimental findings revealed that ATA employs multiple modes of action to inhibit PMCA activity, which are influenced by ATP but also by the presence of calcium and magnesium ions. Specifically, magnesium appears to enhance this inhibitory effect. Our experimental and in-silico results suggest that, unlike those reported in other proteins, ATA complexed with magnesium (ATA·Mg) is the molecule that inhibits PMCA. In summary, our study presents a novel perspective and establishes a solid foundation for future research efforts aimed at the development of new pharmacological molecules both for PMCA and other proteins.
摘要：
我们的研究旨在阐明金羧酸（ATA）抑制质膜Ca2-ATPase（PMCA）的机制，负责钙运输的关键酶。鉴于PMCA在细胞钙稳态中的关键作用，了解它是如何被ATA抑制的，对于潜在的调节该泵参与的生理病理细胞过程具有重要意义。我们的实验发现表明，ATA采用多种作用方式来抑制PMCA活性，受ATP的影响，也受钙和镁离子的影响。具体来说,镁似乎增强了这种抑制作用。我们的实验和计算机模拟结果表明，与其他蛋白质中报道的不同，与镁复合的ATA（ATA·Mg）是抑制PMCA的分子。总之,我们的研究提出了一个新的观点，并为未来旨在开发PMCA和其他蛋白质的新药理分子的研究工作奠定了坚实的基础。
