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氮唑类抗真菌药物靶酶CYP51的研究进展

李冉 张大志

李冉, 张大志. 氮唑类抗真菌药物靶酶CYP51的研究进展[J]. 药学实践与服务, 2016, 34(2): 106-109. doi: 10.3969/j.issn.1006-0111.2016.02.003
引用本文: 李冉, 张大志. 氮唑类抗真菌药物靶酶CYP51的研究进展[J]. 药学实践与服务, 2016, 34(2): 106-109. doi: 10.3969/j.issn.1006-0111.2016.02.003
LI Ran, ZHANG Dazhi. Development in research of CYP51 as the target of triazoles[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(2): 106-109. doi: 10.3969/j.issn.1006-0111.2016.02.003
Citation: LI Ran, ZHANG Dazhi. Development in research of CYP51 as the target of triazoles[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(2): 106-109. doi: 10.3969/j.issn.1006-0111.2016.02.003

氮唑类抗真菌药物靶酶CYP51的研究进展

doi: 10.3969/j.issn.1006-0111.2016.02.003

Development in research of CYP51 as the target of triazoles

  • 摘要: 氮唑类药物是临床上应用最广、种类最多的广谱高效抗真菌药物,其作用靶点为真菌甾醇合成过程中的一个关键酶——羊毛甾醇14α-去甲基化酶(CYP51)。CYP51由CYP 51基因(同名ERG 11)表达。一方面,真菌CYP51是跨膜蛋白,难以纯化获得其准确的结构信息,成为药物研发的瓶颈之一;另一方面,CYP51变异是公认的真菌耐药的主要原因之一,研究其结构变化对于抗真菌耐药具有重要意义。因此,笔者对近年来CYP51的研究进展进行综述。
  • [1] Lepesheva GI, Waterman MR. Sterol 14alpha-demethylase(cyp51) as a therapeutic target for human trypanosomiasis and leishmaniasis[J]. Curr Top Med Chem, 2011, 11(16):2060-2071.
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    [15] Eddouzi J, Parker JE, Vale-Silva LA, et al. Molecular mechanisms of drug resistance in clinical Candida species isolated from Tunisian hospitals[J].Antimicrob Agents Chemother, 2013, 57(7):3182-3193.
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    [17] Marichal P, Koymans L, Willemsens S, et al. Contribution of mutations in the cytochrome P45014alpha-demethylase(Erg11p, Cyp51p) to azole resistance in Candida albicans[J]. Microbiology, 1999, 145:2701-2713.
    [18] Kudo M, Ohi M, Aoyama Y, et al. Effects of Y132H and F145L substitutions on the activity, azole resistance and spectral properties of Candida albicans sterol 14-demethylase P450(CYP51):a live example showing the selection of altered P450 through interaction with environmental compounds[J]. J Biochem, 2005, 137(5):625-632.
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    [20] Warrilow AG, Martel CM, Parker JE, et al. Azole binding properties of Candida albicans sterol 14-alpha demethylase(CaCYP51)[J]. Antimicrob Agents Chemother, 2010, 54(10):4235-4245.
    [21] Warrilow AG, Mullins JG, Hull CM, et al. S279 point mutations in Candida albicans sterol 14-alpha demethylase(CYP51) reduce in vitro inhibition by fluconazole[J]. Antimicrob Agents Chemother, 2012, 56(4):2099-2107.
    [22] Kelly SL, Lamb DC, Loeffler J, et al. The G464S amino acid substitution in Candida albicans sterol 14alpha-demethylase causes fluconazole resistance in the clinic through reduced affinity[J]. Biochem Biophys Res Commun, 1999, 262(1):174-179.
    [23] Lamb DC, Kelly DE, White TC, et al. The R467K amino acid substitution in Candida albicans sterol 14alpha-demethylase causes drug resistance through reduced affinity[J]. Antimicrob Agents Chemother, 2000, 44(1):63-67.
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    [26] Garcia EG, Mellado E, Gomez-Lopez A, et al. Differences in interactions between azole drugs related to modifications in the 14-alpha sterol demethylase gene(Cyp51A) of Aspergillus fumigatus[J]. Antimicrob Agents Chemother, 2005, 49(5):2119-2121.
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氮唑类抗真菌药物靶酶CYP51的研究进展

doi: 10.3969/j.issn.1006-0111.2016.02.003

摘要: 氮唑类药物是临床上应用最广、种类最多的广谱高效抗真菌药物,其作用靶点为真菌甾醇合成过程中的一个关键酶——羊毛甾醇14α-去甲基化酶(CYP51)。CYP51由CYP 51基因(同名ERG 11)表达。一方面,真菌CYP51是跨膜蛋白,难以纯化获得其准确的结构信息,成为药物研发的瓶颈之一;另一方面,CYP51变异是公认的真菌耐药的主要原因之一,研究其结构变化对于抗真菌耐药具有重要意义。因此,笔者对近年来CYP51的研究进展进行综述。

English Abstract

李冉, 张大志. 氮唑类抗真菌药物靶酶CYP51的研究进展[J]. 药学实践与服务, 2016, 34(2): 106-109. doi: 10.3969/j.issn.1006-0111.2016.02.003
引用本文: 李冉, 张大志. 氮唑类抗真菌药物靶酶CYP51的研究进展[J]. 药学实践与服务, 2016, 34(2): 106-109. doi: 10.3969/j.issn.1006-0111.2016.02.003
LI Ran, ZHANG Dazhi. Development in research of CYP51 as the target of triazoles[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(2): 106-109. doi: 10.3969/j.issn.1006-0111.2016.02.003
Citation: LI Ran, ZHANG Dazhi. Development in research of CYP51 as the target of triazoles[J]. Journal of Pharmaceutical Practice and Service, 2016, 34(2): 106-109. doi: 10.3969/j.issn.1006-0111.2016.02.003
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