Sazanov Leonid A, Hinchliffe Philip
Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, U.K.
Science. 2006 Mar 10;311(5766):1430-6. doi: 10.1126/science.1123809. Epub 2006 Feb 9.
Respiratory complex I plays a central role in cellular energy production in bacteria and mitochondria. Its dysfunction is implicated in many human neurodegenerative diseases, as well as in aging. The crystal structure of the hydrophilic domain (peripheral arm) of complex I from Thermus thermophilus has been solved at 3.3 angstrom resolution. This subcomplex consists of eight subunits and contains all the redox centers of the enzyme, including nine iron-sulfur clusters. The primary electron acceptor, flavin-mononucleotide, is within electron transfer distance of cluster N3, leading to the main redox pathway, and of the distal cluster N1a, a possible antioxidant. The structure reveals new aspects of the mechanism and evolution of the enzyme. The terminal cluster N2 is coordinated, uniquely, by two consecutive cysteines. The novel subunit Nqo15 has a similar fold to the mitochondrial iron chaperone frataxin, and it may be involved in iron-sulfur cluster regeneration in the complex.
呼吸链复合体I在细菌和线粒体的细胞能量产生中起着核心作用。其功能障碍与许多人类神经退行性疾病以及衰老有关。嗜热栖热菌复合体I亲水区（外周臂）的晶体结构已在3.3埃分辨率下解析出来。该亚复合体由八个亚基组成，包含该酶的所有氧化还原中心，包括九个铁硫簇。主要电子受体黄素单核苷酸与簇N3处于电子转移距离内，通向主要氧化还原途径，与远端簇N1a也处于电子转移距离内，N1a可能是一种抗氧化剂。该结构揭示了该酶机制和进化的新方面。末端簇N2由两个连续的半胱氨酸独特地配位。新亚基Nqo15具有与线粒体铁伴侣蛋白frataxin相似的折叠结构，可能参与复合体中铁硫簇的再生。
