P-糖蛋白(P-gp或ABCB1)是ABC转运蛋白广泛家族的成员。P-gp参与生理屏障的建立,限制细胞进入大量有毒化合物。因此,其在这些化合物的药代动力学中起重要作用。癌细胞和被病毒感染的细胞利用P-gp的存在来抵御药物治疗,使它们具有多重抗药性。克服由ABC转运蛋白表达引起的多药耐药性在药物开发领域越来越受到重视。最近,P-gp的研究,特别是通过低温电子显微镜和X射线晶体学进行的结构研究,为该运输机的功能提供了高分辨率的机械细节。各种底物和抑制剂结合形式的分辨率和准确性不断提高的结构可用于分析,并且对底物多特异性机制的共识正在出现。新结构信息的使用可能有助于开发P-gp抑制剂以及可能绕过P-gp作用的化合物。
P-glycoprotein (P-gp or ABCB1) is a member of the broad family of ABC transporters. P-gp participates in the establishment of physiological barriers limiting cellular access of a large number of toxic compounds. It thus plays important roles in the pharmacokinetics of these compounds. Cancer cells and cells infected by viruses exploit the presence of P-gp to fend off drug treatment, rendering them multidrug-resistant. Overcoming multidrug resistance caused by expression of ABC transporters has gained increasing attention in the field of drug development. Recently, studies of P-gp, especially from structural investigations by both cryo-electron microscopy and X-ray crystallography, have provided high-resolution mechanistic details for the function of this transporter. Structures with increasing resolution and accuracy in various substrate- and inhibitor-bound forms are available for analysis and a
consensus on the mechanism of substrate polyspecificity is emerging. The use of new structural information may aid development of P-gp inhibitors as well as compounds that may bypass P-gp action.