Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA; Institute for Structural Biology, Drug Discovery, and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23219, USA.
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA; Institute for Structural Biology, Drug Discovery, and Development, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23219, USA.
Biochim Biophys Acta Biomembr. 2022 Feb 1;1864(1):183793. doi: 10.1016/j.bbamem.2021.183793. Epub 2021 Oct 13.
Mycobacterial membrane protein large 3 (Mmpl3) as a trehalose monomycolate lipid transporter contributes to cell wall biosynthesis. Inhibition of Mmpl3 can suppress cell growth and lead to mycobacterial death. SQ109 is a hydrophobic inhibitor of Mmpl3. We have devised a detergent-free strategy to characterize the SQ109/Mmpl3 interaction using the Native Cell Membrane Nanoparticles (NCMN) system, a new method for extracting membrane proteins that better retains native lipids. The homogeneity of the Mmpl3 NCMN particles was confirmed with electron microscopy. The hydrophobic protein-ligand interaction analysis shown for Mmpl3 using the NCMN system may broadly apply to other membrane proteins.
分枝杆菌膜蛋白大型 3（Mmpl3）作为海藻糖单胞酸酯脂质转运蛋白，有助于细胞壁生物合成。抑制 Mmpl3 可以抑制细胞生长并导致分枝杆菌死亡。SQ109 是 Mmpl3 的一种疏水抑制剂。我们设计了一种无去污剂策略，使用 Native Cell Membrane Nanoparticles（NCMN）系统来表征 SQ109/Mmpl3 相互作用，这是一种提取更好地保留天然脂质的膜蛋白的新方法。电镜证实了 Mmpl3 的 NCMN 颗粒的均一性。使用 NCMN 系统对 Mmpl3 进行的疏水性蛋白-配体相互作用分析可能广泛适用于其他膜蛋白。
