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[致病真菌的ABC转运蛋白:功能分析的最新进展]

[ABC transporters of pathogenic fungi: recent advances in functional analyses].

作者信息

Niimi Masakazu, Tanabe Koichi, Wada Shun-ichi, Yamazaki Akiko, Uehara Yoshimasa, Niimi Kyoko, Lamping Erwin, Holmes Ann R, Monk Brian C, Cannon Richard D

机构信息

Department of Bioactive Molecules, National Institute of Infectious Diseases, Tokyo, Japan.

出版信息

Nihon Ishinkin Gakkai Zasshi. 2005;46(4):249-60. doi: 10.3314/jjmm.46.249.

Abstract

ABC (ATP binding cassette) transporters consist of transmembrane domains which confer specificity, and structurally conserved nucleotide binding domains that contain highly conserved amino acid motifs. They act not only as transporters but also as receptors or channels that use energy generated by ATP hydrolysis. ABC transporters are widely dispersed in nature. They are found in cells ranging from prokaryotes (bacteria) to eukaryotes (including humans) and several are considered to play crucial roles in cellular homeostasis. Defects in ABC transporters in humans are associated with severe diseases such as type 2 diabetes and cystic fibrosis. Some ABC transporters extrude xenobiotics and confer resistance to chemotherapeutics on microbial pathogens and cancer cells. Thus ABC transporters are of considerable medical importance. Structure-function analysis of ABC transporters has begun to elucidate their mechanisms of substrate recognition, the functional regulation of ATP-binding and hydrolysis and to identify intrinsic physiological functions. In pathogenic fungi, ABC transporters contribute to the clinical problem of drug resistance. The application of new technologies to the examination of fungal ABC transporter function is providing new insights into the use of antifungal drugs in medical mycology and contributing to a better understanding of these important membrane proteins.

摘要

ABC(ATP结合盒)转运蛋白由赋予特异性的跨膜结构域和含有高度保守氨基酸基序的结构保守的核苷酸结合结构域组成。它们不仅作为转运蛋白发挥作用,还作为利用ATP水解产生的能量的受体或通道。ABC转运蛋白在自然界中广泛分布。它们存在于从原核生物(细菌)到真核生物(包括人类)的细胞中,并且有几种被认为在细胞内稳态中起关键作用。人类ABC转运蛋白的缺陷与严重疾病如2型糖尿病和囊性纤维化有关。一些ABC转运蛋白可排出外源性物质,并赋予微生物病原体和癌细胞对化疗药物的抗性。因此,ABC转运蛋白具有相当重要的医学意义。ABC转运蛋白的结构 - 功能分析已开始阐明其底物识别机制、ATP结合和水解的功能调节,并确定其内在生理功能。在致病真菌中,ABC转运蛋白导致耐药性这一临床问题。将新技术应用于真菌ABC转运蛋白功能的研究,为医学真菌学中抗真菌药物的使用提供了新的见解,并有助于更好地理解这些重要的膜蛋白。

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