Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125 Bari, Italy.
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Via Orabona 4, 70125 Bari, Italy; CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), Via Amendola 122/O, 70126 Bari, Italy.
Biochim Biophys Acta Bioenerg. 2022 Jun 1;1863(5):148557. doi: 10.1016/j.bbabio.2022.148557. Epub 2022 Apr 1.
We herein report the identification of the lantanide praseodymium trivalent ion Pr as inhibitor of mitochondrial transporters for basic amino acids and phylogenetically related carriers belonging to the Slc25 family. The inhibitory effect of Pr has been tested using mitochondrial transporters reconstituted into liposomes being effective in the micromolar range, acting as a competitive inhibitor of the human basic amino acids carrier (BAC, Slc25A29), the human carnitine/acylcarnitine carrier (CAC, Slc25A20). Furthermore, we provide computational evidence that the complete inhibition of the transport activity of the recombinant proteins is due to the Pr coordination to key acidic residues of the matrix salt bridge network. Besides being used as a first choice stop inhibitor for functional studies in vitro of mitochondrial carriers reconstituted in proteoliposomes, Pr might also represent a useful tool for structural studies of the mitochondrial carrier family.
我们在此报告镧系元素镨离子 Pr 作为线粒体转运蛋白抑制剂的鉴定，这些转运蛋白用于基本氨基酸和系统发育相关的载体属于 Slc25 家族。使用重组到脂质体中的线粒体转运蛋白测试了 Pr 的抑制作用，其在微摩尔范围内有效，作为人碱性氨基酸载体 (BAC，Slc25A29) 和人肉碱/酰基辅酶 A 载体 (CAC，Slc25A20) 的竞争性抑制剂。此外，我们提供了计算证据，表明重组蛋白的转运活性完全抑制是由于 Pr 与基质盐桥网络的关键酸性残基配位。除了作为体外重组蛋白功能研究的首选停止抑制剂外，Pr 也可能是研究线粒体载体家族结构的有用工具。
