哺乳動(dòng)物脂肪酸合酶是人體細(xì)胞中最復(fù)雜的分子合成機(jī)器之一,，同時(shí)它也是抗癌藥,、抗肥胖藥及代謝紊亂治療的有希望的標(biāo)靶,。瑞士科學(xué)家近日確定了一個(gè)哺乳動(dòng)物脂肪酸合酶的原子結(jié)構(gòu),。相關(guān)論文發(fā)表在《科學(xué)》（Science）雜志上。
脂肪酸的合成是一個(gè)重要的細(xì)胞過(guò)程,，脂肪酸在細(xì)胞中被用作能量存儲(chǔ)化合物、信使分子及細(xì)胞外被膜的構(gòu)造材料,。在除植物外的高等有機(jī)體中,，脂肪酸的合成由大型多功能蛋白進(jìn)行催化,，在這些蛋白中，許多單個(gè)的酶聚集在一起形成“分子裝配線”,。
在最新的研究中,，瑞士蘇黎世工學(xué)院的科學(xué)家根據(jù)收集到的數(shù)據(jù)確定了哺乳動(dòng)物脂肪酸合酶的原子結(jié)構(gòu)。這一結(jié)果揭示了迭代脂肪酸合酶所有的催化活性位點(diǎn),，并說(shuō)明了這種大型酶系統(tǒng)的靈活性如何被用于將酶作用物從一個(gè)活性位點(diǎn)轉(zhuǎn)移至下一個(gè),。新結(jié)構(gòu)的確定被認(rèn)為是該領(lǐng)域研究的里程碑。
動(dòng)物實(shí)驗(yàn)顯示,，抑制哺乳動(dòng)物脂肪酸合酶功能的化合物能夠引起體重降低,，這顯示出脂肪酸合酶潛在的治療肥胖及肥胖相關(guān)性疾病的能力。另外,，由于癌細(xì)胞中對(duì)脂肪酸合成需求的不斷增加,，脂肪酸合酶的抑制劑具有抗癌活性，這使得脂肪酸合酶成為抗癌治療的一個(gè)吸引人的藥靶,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
