哺乳动物脂肪酸合酶是人体细胞中最复杂的分子合成机器之一，同时它也是抗癌药、抗肥胖药及代谢紊乱治疗的有希望的标靶。瑞士科学家近日确定了一个哺乳动物脂肪酸合酶的原子结构。相关论文发表在《科学》（Science）杂志上。
脂肪酸的合成是一个重要的细胞过程，脂肪酸在细胞中被用作能量存储化合物、信使分子及细胞外被膜的构造材料。在除植物外的高等有机体中，脂肪酸的合成由大型多功能蛋白进行催化，在这些蛋白中，许多单个的酶聚集在一起形成“分子装配线”。
在最新的研究中，瑞士苏黎世工学院的科学家根据收集到的数据确定了哺乳动物脂肪酸合酶的原子结构。这一结果揭示了迭代脂肪酸合酶所有的催化活性位点，并说明了这种大型酶系统的灵活性如何被用于将酶作用物从一个活性位点转移至下一个。新结构的确定被认为是该领域研究的里程碑。
动物实验显示，抑制哺乳动物脂肪酸合酶功能的化合物能够引起体重降低，这显示出脂肪酸合酶潜在的治疗肥胖及肥胖相关性疾病的能力。另外，由于癌细胞中对脂肪酸合成需求的不断增加，脂肪酸合酶的抑制剂具有抗癌活性，这使得脂肪酸合酶成为抗癌治疗的一个吸引人的药靶。（生物谷Bioon.com）
生物谷推荐原始出处：
Science，Vol. 321. no. 5894, pp. 1315 – 1322，Timm Maier，Nenad Ban
The Crystal Structure of a Mammalian Fatty Acid Synthase
Timm Maier, Marc Leibundgut, Nenad Ban*
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.
