Cited by 765Enzyme Structure and FunctionMetalloenzymes and iron-sulfur proteinsMitochondrial Function and Pathology

Structure of the Hydrophilic Domain of Respiratory Complex I from Thermus thermophilus

Sazanov, Leonid A., Hinchliffe, Philip·2006·Science

Abstract

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.

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Crossref · 10.1126/science.1123809

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  • Modeling using prokaryotic complex I structures produced an orthologous mammalian core structure containing ND3 Cys39.

    “We modeled the location of ND3 Cys39 using structures of prokaryotic complex I (refs. 32–34). This modeling led to an orthologous mammalian core structure containing ND3 Cys39 (Fig. 3f,g and Supplementary Figs. 14 and 15).”

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Authors
Sazanov, L. A., & Hinchliffe, P.
Affiliations
MRC Mitochondrial Biology Unit (GB)
Corresponding author
Sazanov, Leonid A.
Venue
Science
Published
2006-03-10
Volume
311
Issue
5766
Pages
1430-1436
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W1983737836
Cited by
763
References
49
Citations by year
2026: 7 · 2025: 15 · 2024: 28 · 2023: 14 · 2022: 20 · 2021: 22 · 2020: 26 · 2019: 24 · 2018: 29 · 2017: 28 · 2016: 35 · 2015: 34 · 2014: 41 · 2013: 51 · 2012: 60
FWCI
40.15
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
  • Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
mitochondrial complex I, NADH dehydrogenase, Thermus thermophilus, hydrophilic domains, iron-sulfur clusters, flavin mononucleotide, electron transfer, frataxin, crystal structure, enzyme evolution
MeSH terms
Frataxin, Animals, Bacterial Proteins, Binding Sites, Oxidation-Reduction, Protein Conformation, Thermus thermophilus, Protein Structure, Tertiary, Protein Folding, Crystallography, X-Ray, Protein Subunits, Iron-Binding Proteins, Electron Transport Complex I

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