Molecular basis of multidrug transport by ATP-binding cassette transporters: a proposed two-cylinder engine model.

Molecular basis of multidrug transport by ATP-binding cassette transporters: a proposed two-cylinder engine model.
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ATP 结合盒转运蛋白多药物转运的分子基础:提出的两缸发动机模型。

DOI:
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发表时间:
2001
影响因子:
1.2
通讯作者:
W. Konings
W. Konings
中科院分区:
生物4区
文献类型:
--
作者:
H. W. Veen;Christopher F Higgins;W. Konings

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ATP结合盒多药转运蛋白可能存在于所有活细胞中,并且能够以ATP水解为代价输出各种结构无关的化合物。这些蛋白质在多药耐药细胞中的表达升高会干扰对癌症和传染性病原微生物的药物控制。多药转运蛋白直接与药物底物相互作用。对药物分子和转运蛋白中这种相互作用所需的结构元件的深入了解现在开始出现。然而,关于转运蛋白中药物结合位点的性质和数量,以及ATP水解与药物结合位点的亲和力和/或可及性变化相结合的机制,仍有许多有待了解。本文综述了人类多药耐药P-糖蛋白及其原核同源物LmrA在回答这些问题方面的最新进展。其他ATP结合盒转运这些研究结果的相关性将进行讨论。
ATP-binding cassette multidrug transporters are probably present in all living cells, and are able to export a variety of structurally unrelated compounds at the expense of ATP hydrolysis. The elevated expression of these proteins in multidrug resistant cells interferes with the drug-based control of cancers and infectious pathogenic microorganisms. Multidrug transporters interact directly with the drug substrates. Insights into the structural elements in drug molecules and transport proteins that are required for this interaction are now beginning to emerge. However, much remains to be learned about the nature and number of drug binding sites in the transporters, and the mechanism(s) by which ATP hydrolysis is coupled to changes in affinity and/or accessibility of drug binding sites. This review summarizes recent advances in answering these questions for the human multidrug resistance P-glycoprotein and its prokaryotic homolog LmrA. The relevance of these findings for other ATP-binding cassette transporters will be discussed.
DOI: 10.1152/physrev.1999.79.1.s77
发表时间: 1999
影响因子: 33.6
作者:
D. Gadsby;A. Nairn
通讯作者: D. Gadsby;A. Nairn
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DOI: 10.1046/j.1432-1327.1998.2550383.x
发表时间: 1998
期刊: European journal of biochemistry
影响因子: --
作者:
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发表时间: 1997-11-25
影响因子: 11.1
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发表时间: 1998-01-20
期刊: BIOCHEMISTRY
影响因子: 2.9
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