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恶性疟原虫硫氧还蛋白还原酶(PfTrxR)及其作为新型抗疟药物靶点的作用

Plasmodium falciparum Thioredoxin Reductase (PfTrxR) and Its Role as a Target for New Antimalarial Discovery.

作者信息

McCarty Sara E, Schellenberger Amanda, Goodwin Douglas C, Fuanta Ngolui Rene, Tekwani Babu L, Calderón Angela I

机构信息

College of Sciences and Mathematics, Auburn University, Auburn, AL 36849, USA.

Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA.

出版信息

Molecules. 2015 Jun 22;20(6):11459-73. doi: 10.3390/molecules200611459.

Abstract

The growing resistance to current antimalarial drugs is a major concern for global public health. The pressing need for new antimalarials has led to an increase in research focused on the Plasmodium parasites that cause human malaria. Thioredoxin reductase (TrxR), an enzyme needed to maintain redox equilibrium in Plasmodium species, is a promising target for new antimalarials. This review paper provides an overview of the structure and function of TrxR, discusses similarities and differences between the thioredoxin reductases (TrxRs) of different Plasmodium species and the human forms of the enzyme, gives an overview of modeling Plasmodium infections in animals, and suggests the role of Trx functions in antimalarial drug resistance. TrxR of Plasmodium falciparum is a central focus of this paper since it is the only Plasmodium TrxR that has been crystallized and P. falciparum is the species that causes most malaria cases. It is anticipated that the information summarized here will give insight and stimulate new directions in which research might be most beneficial.

摘要

当前抗疟药物耐药性的不断增加是全球公共卫生的一个主要关注点。对新型抗疟药物的迫切需求导致了针对引起人类疟疾的疟原虫的研究增加。硫氧还蛋白还原酶(TrxR)是疟原虫物种维持氧化还原平衡所需的一种酶,是新型抗疟药物的一个有前景的靶点。这篇综述文章概述了TrxR的结构和功能,讨论了不同疟原虫物种的硫氧还蛋白还原酶(TrxRs)与该酶的人类形式之间的异同,概述了在动物中模拟疟原虫感染的情况,并提出了Trx功能在抗疟药物耐药性中的作用。恶性疟原虫的TrxR是本文的核心关注点,因为它是唯一已被结晶的疟原虫TrxR,且恶性疟原虫是导致大多数疟疾病例的物种。预计这里总结的信息将提供见解并激发最具研究价值的新方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f39c/6272602/90573e1dac2b/molecules-20-11459-g001.jpg

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