2006/02/09 by Leonid A. Sazanov, Philip Hinchliffe · 7 citations
Biochemistry, Genetics and Molecular Biology · Energy · #Mitochondrial Function and Pathology #Photosynthetic Processes and Mechanisms #Metalloenzymes and iron-sulfur proteins
paper · doi:10.1126/science.1123809
openalex publication_date 2006/02/09 · openalex created_date 2016/06/24 · openalex updated_date 2026/07/28
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.