The Structure and Mechanism of Drug Transporters.
The Structure and Mechanism of Drug Transporters.
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DOI：
10.1007/978-1-0716-1554-6_8
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Roberts AG
中科院分区：
文献类型：
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作者：
Roberts AG
药物转运蛋白是一种重要的膜蛋白，通过影响药物的吸收、分布和排泄，在药物的处置过程中发挥着重要作用。它们利用ATP水解或离子/浓度梯度跨膜转运药物以及内源性分子和毒素。一般来说，药物转运蛋白普遍表达，但它们在药物处置中的功能是通过集中在组织如肠、肾、肝和脑中来实现的。根据其一级序列和作用机制，转运蛋白可分为ATP结合盒（ABC）、溶质连接载体（SLC）和溶质载体有机阴离子（SLCO）超家族。许多X射线晶体学和冷冻电子显微镜（cryo-EM）结构已经在ABC和SLC转运蛋白超家族或其细菌同系物中得到解决。这些结构为深入了解运输的结构基础提供了宝贵的见解。本章将特别关注混杂药物转运蛋白，因为它们对药物处置的影响以及与之相关的挑战。
Drug transporters are integral membrane proteins that play a critical role in drug disposition by affecting absorption, distribution, and excretion. They translocate drugs, as well as endogenous molecules and toxins, across membranes using ATP hydrolysis, or ion/concentration gradients. In general, drug transporters are expressed ubiquitously, but they function in drug disposition by being concentrated in tissues such as the intestine, the kidneys, the liver, and the brain. Based on their primary sequence and their mechanism, transporters can be divided into the ATP-Binding Cassette (ABC), Solute-Linked Carrier (SLC), and the SoLute Carrier Organic anion (SLCO) superfamilies. Many X-ray crystallography and cryo-electron microscopy (cryo-EM) structures have been solved in the ABC and SLC transporter superfamilies or of their bacterial homologs. The structures have provided valuable insight into the structural basis of transport. This chapter will provide particular focus on the promiscuous drug transporters because of their effect on drug disposition and the challenges associated with them.