Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
FEBS Lett. 2021 Mar;595(6):750-762. doi: 10.1002/1873-3468.14054. Epub 2021 Feb 28.
P-glycoprotein (P-gp, ABCB1) is an ABC transporter associated with the development of multidrug resistance to chemotherapy. During its catalytic cycle, P-gp undergoes significant conformational changes. Recently, atomic structures of some of these conformations have been resolved using cryo-electron microscopy. The ATP hydrolysis-defective mutant of the catalytic glutamate residue of the Walker B motif (E556Q/E1201Q) has been used to determine the structure of the ATP-bound inward-closed conformation of P-gp. Here, we show that this mutant does not appear to undergo the same steps as wild-type P-gp. We discuss conformational differences in the EQ mutant that may lead to a better understanding of the catalytic cycle of P-gp and propose that additional structural studies with wild-type P-gp are required.
P-糖蛋白（P-gp，ABCB1）是一种与化疗多药耐药性发展相关的 ABC 转运蛋白。在其催化循环中，P-gp 经历了显著的构象变化。最近，使用冷冻电子显微镜解析了其中一些构象的原子结构。Walker B 基序催化谷氨酸残基的 ATP 水解缺陷突变体（E556Q/E1201Q）已被用于确定 P-gp 的 ATP 结合的内向闭合构象的结构。在这里，我们表明该突变体似乎不会经历与野生型 P-gp 相同的步骤。我们讨论了 EQ 突变体中的构象差异，这可能有助于更好地理解 P-gp 的催化循环，并提出需要对野生型 P-gp 进行更多的结构研究。
