Structural and dynamical rationale for fatty acid unsaturation in Escherichia coli
Structural and dynamical rationale for fatty acid unsaturation in Escherichia coli
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DOI：
10.1073/pnas.1818686116
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发表时间：
2019-04-02
影响因子：
11.1
通讯作者：
Burkart, Michael D.
中科院分区：
文献类型：
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作者：
Dodge, Greg J.;Patel, Ashay;Burkart, Michael D.
A-和y-蛋白细菌的脂肪酸生物合成需要两种功能不同的脱水酶：FabA和FabZ。在这里，机械交联有助于稳定的六聚体复合体的结构表征，该复合体由六个大肠杆菌FabZ脱水酶亚基和六个AcpP酰基载体蛋白组成。这种晶体结构揭示了蚕豆和FabZ的发散底物选择性，揭示了结合口袋的不同结构。分子动力学模拟表明，FabA和FabZ活性中心的底物取向和构象存在差异，使得FabZ预先组织成只催化脱水，而FabA既可以催化脱水，也可以进行异构化。
Fatty acid biosynthesis in a- and y-proteobacteria requires two functionally distinct dehydratases, FabA and FabZ. Here, mechanistic cross-linking facilitates the structural characterization of a stable hexameric complex of six Escherichia coli FabZ dehydratase subunits with six AcpP acyl carrier proteins. The crystal structure sheds light on the divergent substrate selectivity of FabA and FabZ by revealing distinct architectures of the binding pocket. Molecular dynamics simulations demonstrate differential biasing of substrate orientations and conformations within the active sites of FabA and FabZ such that FabZ is preorganized to catalyze only dehydration, while FabA is primed for both dehydration and isomerization.