细胞内一种称为脂肪酸合成酶的分子复合体合成脂肪。美国儿童医院奥克兰研究所Stuart Smith博士与来自加州Scripps研究所的研究人员合作，详细报道该酶复合体如何相互协作合成脂肪。该复合体很有可能成为开发新一代抗肥胖和抗癌症药物的靶标。这项研究发表在2 月Nature Structural and Molecular Biology杂志上。
Smith 博士表示，脂肪酸合成酶拥有一种相当复杂的结构。此前预期该酶复合体结构相当柔性，因而很难利用X 光晶体衍射分析这种复合体结构。2008 年，瑞士一组研究人员解析了该复合体的X 光衍射结构，但仅提供了众多构型中的一个。近期的研究利用最前沿的电子显微镜捕获脂肪酸合成酶众多不同构型的图片，将这些图片以适当方式动态排列，从而可以全程显示该酶复合体不同构型的运动。结果显示，位于该酶复合体X 光结构中边远位置的多种酶可以始终与参与催化的酶保持接触。
部分制药公司聚焦于脂肪酸合成酶抑制剂的开发，后者阻断碳水化合物向脂肪转化，抑制胃口，并延缓癌症细胞的生长。来自X 光和电子显微镜图像的结构信息，将有助于具有治疗价值的高效抑制剂设计。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Structural & Molecular Biology 18 January 2009 | doi:10.1038/nsmb.1532
Conformational flexibility of metazoan fatty acid synthase enables catalysis
Edward J Brignole1, Stuart Smith2 & Francisco J Asturias1
Abstract
The metazoan cytosolic fatty acid synthase (FAS) contains all of the enzymes required for de novo fatty acid biosynthesis covalently linked around two reaction chambers. Although the three-dimensional architecture of FAS has been mostly defined, it is unclear how reaction intermediates can transfer between distant catalytic domains. Using single-particle EM, we have identified a near continuum of conformations consistent with a remarkable flexibility of FAS. The distribution of conformations was influenced by the presence of substrates and altered by different catalytic mutations, suggesting a direct correlation between conformation and specific enzymatic activities. We interpreted three-dimensional reconstructions by docking high-resolution structures of individual domains, and they show that the substrate-loading and condensation domains dramatically swing and swivel to access substrates within either reaction chamber. Concomitant rearrangement of the -carbon–processing domains synchronizes acyl chain reduction in one chamber with acyl chain elongation in the other.
1 Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
2 Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, California 94609, USA.
