Mycobacterium tuberculosis Exploits a Heterohexameric Enoyl-CoA Hydratase Retro-Aldolase Complex for Cholesterol Catabolism.
Mycobacterium tuberculosis Exploits a Heterohexameric Enoyl-CoA Hydratase Retro-Aldolase Complex for Cholesterol Catabolism.
复制标题
结核分枝杆菌利用异六聚烯酰辅酶 A 水合酶逆醛缩酶复合物进行胆固醇分解代谢。
DOI：
10.1021/acs.biochem.9b00673
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Sampson,NicoleS
中科院分区：
文献类型：
--
作者：
Yuan,Tianao;Yang,Meng;Gehring,Kalle;Sampson,NicoleS
胆固醇分解代谢在结核分枝杆菌（Mtb）在宿主体内的生存和持续中起着重要作用。mtbex利用三个β-氧化循环来完全降解胆固醇的侧链。单个操纵子上的5个顺反子基因编码3种酶，即3-氧-4-孕烯-20-羧基-辅酶a脱氢酶（ChsE1-ChsE2）、3-氧-4,17-孕二烯-20-羧基-辅酶a水合酶（ChsH1-ChsH2）和17-羟基-3-氧-4-孕烯-20-羧基-辅酶a反醛缩酶（Ltp2），完成该途径的最后一个β-氧化循环。在这三种酶中，ChsH1-ChsH2和Ltp2形成了催化碳-碳键切割所需的蛋白质复合物。在这项工作中，我们报告了基于小角x射线散射和单粒子电子显微镜数据的全长ChsH1-ChsH2-Ltp2配合物的结构。诱变实验证实了Ltp2催化逆转录醛醇反应的必要性。该结构说明了酶之间酰基转移是如何发生的。ChsH1-ChsH2-Ltp2复合物的每个原聚体包含三个蛋白质组分：ChsH1链、ChsH2链和Ltp2链。两个原聚体在Ltp2的界面处二聚形成一个异六聚体结构。ChsH1-ChsH2-Ltp2复合物的这种独特的异六聚体结构为进一步了解mtb中胆固醇分解代谢的机制提供了切入点。
Cholesterol catabolism plays an important role inMycobacterium tuberculosis’s (Mtb’s) survival and persistence in the host.Mtbexploits three β-oxidation cycles to fully degrade the side chain of cholesterol. Five cistronic genes in a single operon encode three enzymes, 3-oxo-4-pregnene-20-carboxyl-CoA dehydrogenase (ChsE1-ChsE2), 3-oxo-4,17-pregnadiene-20-carboxyl-CoA hydratase (ChsH1-ChsH2), and 17-hydroxy-3-oxo-4-pregnene-20-carboxyl-CoA retro-aldolase (Ltp2), to perform the last β-oxidation cycle in this pathway. Among these three enzymes, ChsH1-ChsH2 and Ltp2 form a protein complex that is required for the catalysis of carbon–carbon bond cleavage. In this work, we report the structure of the full length ChsH1-ChsH2-Ltp2 complex based on small-angle X-ray scattering and single-particle electron microscopy data. Mutagenesis experiments confirm the requirement for Ltp2 to catalyze the retro-aldol reaction. The structure illustrates how acyl transfer between enzymes may occur. Each protomer of the ChsH1-ChsH2-Ltp2 complex contains three protein components: a chain of ChsH1, a chain of ChsH2, and a chain of Ltp2. Two protomers dimerize at the interface of Ltp2 to form a heterohexameric structure. This unique heterohexameric structure of the ChsH1-ChsH2-Ltp2 complex provides entry to further understand the mechanism of cholesterol catabolism inMtb.