Structural basis for conservation in the CYP51 family.

Structural basis for conservation in the CYP51 family.
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DOI:
10.1016/j.bbapap.2010.06.006
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发表时间:
2011-01
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Waterman MR
Waterman MR
中科院分区:
其他
文献类型:
--
作者:
Lepesheva GI;Waterman MR

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甾醇14去甲基酶(Stol14α-Demthylase,14 DM)是细胞色素P450基因组家族的成员。14-DM反应对于生物合成甾醇是必不可少的,而甾醇是产生细胞膜所必需的。这是分布最广的P450,存在于所有生物界。从一个王国到另一个王国,初级氨基酸序列的同源性通常在30%-20%之间。在这篇简短的综述中,我们描述了特定氨基酸和各种CYP51同源基因的保守,并指出了它们在单加氧酶的结构/功能中可能扮演的角色。对不同氨基酸在14 DM中作用的预测是基于这些酶的高分辨率三级结构,这为详细了解14α-去甲基酶反应及其选择性、门类特异性抑制奠定了基础,这对于设计治疗病原微生物感染的有效抑制剂至关重要。
Sterol 14α-demethylases (14DM) comprise the CYP51 cytochrome P450 genome family. The 14DM reaction is essential for the biosynthesis of sterols which are necessary for production of cellular membranes. This is the most widely distributed P450, being present in all biological kingdoms. From one kingdom to another the primary amino acid sequence identity usually ranges between 30-20%. In this minireview we describe the conservation of specific amino acids and the various CYP51 orthologs and indicate the roles that they may play in the structure/function of this monooxygenase. The prediction of the roles of different amino acids in 14DM is based on high resolution tertiary structures of these enzymes which set the stage for detailed understanding of the 14α-demethylase reaction and its selective, phyla-specific inhibition which is crucial for the design of potent inhibitors for treatment of infection by pathogenic microbes.
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影响因子: 3.9
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