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致病真菌中通过串联重复产生的异常细胞色素 P450 的出现。

Blooming of Unusual Cytochrome P450s by Tandem Duplication in the Pathogenic Fungus .

机构信息

Department of Biochemistry and Microbiology, Faculty of Science and Agriculture, University of Zululand, KwaDlangezwa 3886, South Africa.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

出版信息

Int J Mol Sci. 2018 Jun 9;19(6):1711. doi: 10.3390/ijms19061711.

Abstract

While the Zygomycete fungus primarily infects insects, it can be pathogenic to mammals as well, including humans. High variability in the treatment of this fungal infection with currently available drugs, including azole drugs is a very common phenomenon. Azoles bind to the cytochrome P450 monooxygenases (P450s/CYP) including CYP51, a sterol 14-α-demethylase, inhibiting the synthesis of cell membrane ergosterol and thus leading to the elimination of infecting fungi. Despite P450’s role as a drug target, to date, no information on P450s has been reported. Genome-wide data mining has revealed the presence of 142 P450s grouped into 12 families and 21 subfamilies in . Except for CYP51, the remaining 11 P450 families are new (CYP5854-CYP5864). Despite having a large number of P450s among entomopathogenic fungi, has the lowest number of P450 families, which suggests blooming P450s. Further analysis has revealed that 79% of the same family P450s is tandemly positioned, suggesting that P450 tandem duplication led to the blooming of P450s. The results of this study; i.e., unravelling the P450 content, will certainly help in designing experiments to understand P450s’ role in physiology, including a highly variable response to azole drugs with respect to P450s.

摘要

虽然接合菌真菌主要感染昆虫,但它也可能对哺乳动物致病,包括人类。目前可用药物治疗这种真菌感染的方法存在很大的变异性,包括唑类药物。唑类药物与细胞色素 P450 单加氧酶(P450s/CYP)结合,包括 CYP51,一种甾醇 14-α-脱甲基酶,抑制细胞膜麦角固醇的合成,从而导致感染真菌的消除。尽管 P450 是药物靶点,但迄今为止,尚无关于 P450 的信息报道。全基因组数据挖掘揭示了 142 种 P450 存在于 中,分为 12 个家族和 21 个亚家族。除了 CYP51 之外,其余 11 个 P450 家族都是新的(CYP5854-CYP5864)。尽管昆虫病原真菌中存在大量 P450,但 中 P450 家族的数量最少,这表明 P450 大量存在。进一步分析表明,相同家族 P450 的 79%是串联排列的,这表明 P450 串联重复导致了 P450 的大量存在。这项研究的结果,即揭示 P450 的含量,将有助于设计实验来了解 P450 在 生理学中的作用,包括对唑类药物的高度可变反应与 P450 有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c1f/6032100/947ca4c43a06/ijms-19-01711-g001.jpg

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