Substrate analog studies of the ýý-regiospecificity of Mycobacterium tuberculosis cholesterol metabolizing cytochrome P450 enzymes CYP124A1, CYP125A1 and CYP142A1.
Substrate analog studies of the ýý-regiospecificity of Mycobacterium tuberculosis cholesterol metabolizing cytochrome P450 enzymes CYP124A1, CYP125A1 and CYP142A1.
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结核分枝杆菌胆固醇代谢细胞色素 P450 酶 CYP124A1、CYP125A1 和 CYP142A1 的 α-区域特异性的底物模拟研究。
DOI：
10.1016/j.bmc.2012.05.003
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发表时间：
2012
影响因子：
3.5
通讯作者：
OrtizdeMontellano,PaulR
中科院分区：
文献类型：
--
作者：
Johnston,JonathanB;Singh,ArtiA;Clary,AnaelleA;Chen,Chiung-Kuan;Hayes,PatriciaY;Chow,Sharon;DeVoss,JamesJ;OrtizdeMontellano,PaulR
我们报告了一系列胆固醇侧链类似物的合成和评价，作为三种重要的结核分枝杆菌细胞色素P450酶的机械探针，其选择性氧化甲基分支胆固醇侧链的ω-位置。为了探测对生物学不利的ω-区域特异性的结构要求，我们比较了这些底物类似物与每个P450的结合，确定了转换速率，并表征了酶促产物。结果进行了讨论的上下文中的酶的结构-活性关系，以及它们的活性位点如何执行ω-氧化。
We report the synthesis and evaluation of a series of cholesterol side-chain analogs as mechanistic probes of three important Mycobacterium tuberculosis cytochrome P450 enzymes that selectively oxidize the ω-position of the methyl-branched cholesterol side-chain. To probe the structural requirements for the thermodynamically disfavored ω-regiospecificity we compared the binding of these substrate analogs to each P450, determined the turnover rates, and characterized the enzymatic products. The results are discussed in the context of the structure-activity relationships of the enzymes and how their active sites enforce ω-oxidation.