Basting Daniel, Lehner Ines, Lorch Mark, Glaubitz Clemens
Institute for Biophysical Chemistry, Centre for Biomolecular Magnetic Resonance, J.W. Goethe Universität, Marie-Curie Str. 9, 60439, Frankfurt am Main, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Mar;372(6):451-64. doi: 10.1007/s00210-006-0039-4. Epub 2006 Feb 28.
Transporters form an interesting and complex class of membrane proteins. Many of them are potential drug targets due to their role in translocation of ions, small molecules and peptides across the membrane or due to their role in multidrug resistance. Hence elucidating their structure and mechanism is of great importance and may lead to a host of new drugs and methods to alter or inhibit their function. Solid state NMR is an emerging technique for investigating transport proteins. Along with other biochemical and biophysical techniques solid state NMR can provide data on drug binding, protein dynamics and structure at the interface between structural biology and functional analysis. Here, we review solid state NMR applications to primary active and secondary transporters involved in translocation of small molecules. We discuss current experimental limitations and give an overall perspective on how the technique may be used to address some pertinent questions relevant to transporters.
转运蛋白构成了一类有趣且复杂的膜蛋白。它们中的许多是潜在的药物靶点,这是因为它们在离子、小分子和肽跨膜转运中发挥作用,或者由于它们在多药耐药性中所起的作用。因此,阐明它们的结构和机制非常重要,可能会带来许多新药物以及改变或抑制其功能的方法。固态核磁共振是一种用于研究转运蛋白的新兴技术。与其他生物化学和生物物理技术一起,固态核磁共振可以在结构生物学和功能分析的界面上提供有关药物结合、蛋白质动力学和结构的数据。在这里,我们综述了固态核磁共振在参与小分子转运的初级主动转运蛋白和次级转运蛋白中的应用。我们讨论了当前的实验局限性,并对该技术如何用于解决与转运蛋白相关的一些关键问题给出了总体展望。