On the putative co-transport of drugs by multidrug resistance proteins

被引：58

作者：

Borst, P

Zelcer, N

van de Wetering, K

Poolman, B

机构：

[1] Netherlands Canc Inst, Div Mol Biol, Biomed Genet Ctr, NL-1066 CX Amsterdam, Netherlands

[2] Univ Calif Los Angeles, Dept Pathol & Lab Med, Howard Hughes Med Inst, MacDonald Res Labs, Los Angeles, CA 90095 USA

[3] MSC, Dept Biochem, Groningen Biomol Sci & Biotechnol Inst, NL-9747 AG Groningen, Netherlands

来源：

FEBS LETTERS | 2006年 / 580卷 / 04期

关键词：

ABC transporters; homotropic cooperativity; heterotropic cooperativity; transport kinetics; MRPs;

D O I：

10.1016/j.febslet.2005.12.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Experiments with multidrug resistance-associated protein I (MRP1) showed 10-years ago that transport of vincristine (VCR) by MRP1 could be stimulated by GSH, and transport of GSH by VCR. Since then many examples of stimulated transport have been reported for MRP1, 2, 3, 4 and 8. We discuss here three models to explain stimulated transport. We favour a model in which a large promiscuous binding site can bind more than one ligand, allowing cooperative/competitive interactions between ligands within the binding site. We conclude that there is no unambiguous proof for co-transport of two different ligands by MRPs, but that cross-stimulated transport can explain the published data. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：1085 / 1093

页数：9

共 51 条

[1] Therapeutic and biological importance of getting nucleotides out of cells: a case for the ABC transporters, MRP4 and 5 [J].