The crystal structure of a mammalian fatty acid synthase
The crystal structure of a mammalian fatty acid synthase
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DOI：
10.1126/science.1161269
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发表时间：
2008-09-05
期刊：
影响因子：
56.9
通讯作者：
Ban, Nenad
中科院分区：
文献类型：
--
作者：
Maier, Timm;Leibundgut, Marc;Ban, Nenad
哺乳动物脂肪酸合成酶是一种催化脂肪酸合成所有步骤的大型多酶。我们已经确定了其晶体结构在3.2埃的分辨率，涵盖五个催化域，而灵活拴系的末端酰基载体蛋白和硫酯酶结构域仍未得到解决。该结构揭示了交替接头和酶结构域的复杂结构。底物穿梭通过酰基载体蛋白结构域的柔性拴系以及多酶的缩合和修饰部分之间的有限接触来促进，所述缩合和修饰部分主要通过接头而不是直接相互作用连接。该结构鉴定了两个额外的非酶结构域：（i）假酮还原酶和（ii）外周假甲基转移酶，其可能是一些相关聚酮化合物脱氢酶中保留的祖先甲基转移酶结构域的残基.哺乳动物脂肪酸合酶与模块化聚酮酶的结构比较显示了它们的节段结构如何允许结构域组成的变化以实现多样化的产物合成。
Mammalian fatty acid synthase is a large multienzyme that catalyzes all steps of fatty acid synthesis. We have determined its crystal structure at 3.2 angstrom resolution covering five catalytic domains, whereas the flexibly tethered terminal acyl carrier protein and thioesterase domains remain unresolved. The structure reveals a complex architecture of alternating linkers and enzymatic domains. Substrate shuttling is facilitated by flexible tethering of the acyl carrier protein domain and by the limited contact between the condensing and modifying portions of the multienzyme, which are mainly connected by linkers rather than direct interaction. The structure identifies two additional nonenzymatic domains: ( i) a pseudo- ketoreductase and ( ii) a peripheral pseudo- methyltransferase that is probably a remnant of an ancestral methyltransferase domain maintained in some related polyketide synthases. The structural comparison of mammalian fatty acid synthase with modular polyketide synthases shows how their segmental construction allows the variation of domain composition to achieve diverse product synthesis.