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脂质转运蛋白在真菌生理学和致病性中的作用。

Role of lipid transporters in fungal physiology and pathogenicity.

作者信息

Rizzo Juliana, Stanchev Lyubomir Dimitrov, da Silva Vanessa K A, Nimrichter Leonardo, Pomorski Thomas Günther, Rodrigues Marcio L

机构信息

Instituto de Microbiologia Paulo de Góes (IMPG), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.

Department of Molecular Biochemistry, Ruhr University Bochum, Faculty of Chemistry and Biochemistry, 44780 Bochum, Germany.

出版信息

Comput Struct Biotechnol J. 2019 Sep 4;17:1278-1289. doi: 10.1016/j.csbj.2019.09.001. eCollection 2019.

Abstract

The fungal cell wall and membrane are the most common targets of antifungal agents, but the potential of membrane lipid organization in regulating drug-target interactions has yet to be investigated. Energy-dependent lipid transporters have been recently associated with virulence and drug resistance in many pathogenic fungi. To illustrate this view, we discuss (i) the structural and biological aspects of ATP-driven lipid transporters, comprising P-type ATPases and ATP-binding cassette transporters, (ii) the role of these transporters in fungal physiology and virulence, and (iii) the potential of lipid transporters as targets for the development of novel antifungals. These recent observations indicate that the lipid-trafficking machinery in fungi is a promising target for studies on physiology, pathogenesis and drug development.

摘要

真菌细胞壁和细胞膜是抗真菌药物最常见的作用靶点,但膜脂组织在调节药物-靶点相互作用方面的潜力尚未得到研究。能量依赖性脂质转运蛋白最近已被证明与许多致病真菌的毒力和耐药性有关。为了阐明这一观点,我们讨论了:(i)由P型ATP酶和ATP结合盒转运蛋白组成的ATP驱动脂质转运蛋白的结构和生物学特性;(ii)这些转运蛋白在真菌生理学和毒力中的作用;(iii)脂质转运蛋白作为新型抗真菌药物开发靶点的潜力。这些最新观察结果表明,真菌中的脂质转运机制是生理学、发病机制和药物开发研究的一个有前景的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc3f/6944739/021085b43a37/ga1.jpg

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