PDBsum entry 2gmh

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protein ligands metals Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
581 a.a. *
BHG ×3
SF4 ×2
FAD ×2
UQ5 ×2
EDO ×10
Waters ×369
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Structure of porcine electron transfer flavoprotein- ubiquinone oxidoreductase in complexed with ubiquinone
Structure: Electron transfer flavoprotein-ubiquinone oxidoreductase. Chain: a, b. Synonym: etf-qo, etf-ubiquinone oxidoreductase, etf dehydrogenase, electron-transferring- flavoprotein dehydrogenase, fragment. Ec:
Source: Sus scrofa. Pig. Organism_taxid: 9823
2.50Å     R-factor:   0.221     R-free:   0.254
Authors: J.Zhang,F.E.Frerman,J.-J.P.Kim
Key ref:
J.Zhang et al. (2006). Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool. Proc Natl Acad Sci U S A, 103, 16212-16217. PubMed id: 17050691 DOI: 10.1073/pnas.0604567103
06-Apr-06     Release date:   17-Oct-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P55931  (ETFD_PIG) -  Electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial
617 a.a.
581 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Electron-transferring-flavoprotein dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Reduced electron-transferring flavoprotein + ubiquinone = electron- transferring flavoprotein + ubiquinol
Reduced electron-transferring flavoprotein
Bound ligand (Het Group name = UQ5)
matches with 48.00% similarity
= electron- transferring flavoprotein
+ ubiquinol
      Cofactor: FAD; Iron-sulfur
Bound ligand (Het Group name = FAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     electron carrier activity     9 terms  


DOI no: 10.1073/pnas.0604567103 Proc Natl Acad Sci U S A 103:16212-16217 (2006)
PubMed id: 17050691  
Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool.
J.Zhang, F.E.Frerman, J.J.Kim.
Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is a 4Fe4S flavoprotein located in the inner mitochondrial membrane. It catalyzes ubiquinone (UQ) reduction by ETF, linking oxidation of fatty acids and some amino acids to the mitochondrial respiratory chain. Deficiencies in ETF or ETF-QO result in multiple acyl-CoA dehydrogenase deficiency, a human metabolic disease. Crystal structures of ETF-QO with and without bound UQ were determined, and they are essentially identical. The molecule forms a single structural domain. Three functional regions bind FAD, the 4Fe4S cluster, and UQ and are closely packed and share structural elements, resulting in no discrete structural domains. The UQ-binding pocket consists mainly of hydrophobic residues, and UQ binding differs from that of other UQ-binding proteins. ETF-QO is a monotopic integral membrane protein. The putative membrane-binding surface contains an alpha-helix and a beta-hairpin, forming a hydrophobic plateau. The UQ-flavin distance (8.5 A) is shorter than the UQ-cluster distance (18.8 A), and the very similar redox potentials of FAD and the cluster strongly suggest that the flavin, not the cluster, transfers electrons to UQ. Two possible electron transfer paths can be envisioned. First, electrons from the ETF flavin semiquinone may enter the ETF-QO flavin one by one, followed by rapid equilibration with the cluster. Alternatively, electrons may enter via the cluster, followed by equilibration between centers. In both cases, when ETF-QO is reduced to a two-electron reduced state (one electron at each redox center), the enzyme is primed to reduce UQ to ubiquinol via FAD.
  Selected figure(s)  
Figure 1.
Fig. 1. Ribbon diagram of ETF-QO. The structure comprises three domains: FAD domain (blue), 4Fe4S cluster domain (red), and UQ-binding domain (green). Three redox centers are shown in sticks: FAD (golden yellow), 4Fe4S (magenta), and UQ (dark red). -Helices and -strands are numbered sequentially from the N terminus to the C terminus. The putative membrane-associated surface regions are shown in cyan. Mitochondrial membrane is depicted as blue shaded area.
Figure 4.
Fig. 4. Electrostatic potential surface of ETF-QO viewed from the membrane side. Entrance to the UQ-binding site (dashed circle) and the UQ polyisoprene tail (green sticks) are shown. The surrounding positively charged groups (blue patches) probably are involved in interacting with the negatively charged membrane phospholipid heads. The size of the entrance (dashed circle) is 10 Å x 6 Å and that of the hydrophobic plateau (blue parallelogram) is 24 Å x 30 Å. Color codes are blue for positive (+8 kT), white for neutral, and red for negative (–8 kT).
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21308847 M.A.Swanson, V.Kathirvelu, T.Majtan, F.E.Frerman, G.R.Eaton, and S.S.Eaton (2011).
Electron transfer flavoprotein domain II orientation monitored using double electron-electron resonance between an enzymatically reduced, native FAD cofactor, and spin labels.
  Protein Sci, 20, 610-620.  
21184140 T.Majtan, F.E.Frerman, and J.P.Kraus (2011).
Effect of cobalt on Escherichia coli metabolism and metalloporphyrin formation.
  Biometals, 24, 335-347.  
  19568977 A.M.García, O.Hernández, B.H.Aristizabal, L.A.De Souza Bernardes, R.Puccia, T.W.Naranjo, G.H.Goldman, M.H.Goldman, L.E.Cano, A.Restrepo, and J.G.McEwen (2010).
Gene expression analysis of Paracoccidioides brasiliensis transition from conidium to yeast cell.
  Med Mycol, 48, 147-154.  
19739941 G.Lenaz, and M.L.Genova (2010).
Structure and organization of mitochondrial respiratory complexes: a new understanding of an old subject.
  Antioxid Redox Signal, 12, 961.  
20370797 M.Y.Lan, M.H.Fu, Y.F.Liu, C.C.Huang, Y.Y.Chang, J.S.Liu, C.H.Peng, and S.S.Chen (2010).
High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late-onset lipid storage myopathy.
  Clin Genet, 78, 565-569.  
20533897 P.R.Rich, and A.Maréchal (2010).
The mitochondrial respiratory chain.
  Essays Biochem, 47, 1.  
19282279 M.Kämpf, B.Absmanner, M.Schwarz, and L.Lehle (2009).
Biochemical characterization and membrane topology of Alg2 from Saccharomyces cerevisiae as a bifunctional alpha1,3- and 1,6-mannosyltransferase involved in lipid-linked oligosaccharide biosynthesis.
  J Biol Chem, 284, 11900-11912.  
19487671 M.Marcia, U.Ermler, G.Peng, and H.Michel (2009).
The structure of Aquifex aeolicus sulfide:quinone oxidoreductase, a basis to understand sulfide detoxification and respiration.
  Proc Natl Acad Sci U S A, 106, 9625-9630.
PDB codes: 3h27 3h28 3h29 3hyv 3hyw 3hyx
18296637 J.I.Yeh, U.Chinte, and S.Du (2008).
Structure of glycerol-3-phosphate dehydrogenase, an essential monotopic membrane enzyme involved in respiration and metabolism.
  Proc Natl Acad Sci U S A, 105, 3280-3285.
PDB codes: 2qcu 2r45 2r46 2r4e 2r4j
18836889 N.Gregersen, B.S.Andresen, C.B.Pedersen, R.K.Olsen, T.J.Corydon, and P.Bross (2008).
Mitochondrial fatty acid oxidation defects--remaining challenges.
  J Inherit Metab Dis, 31, 643-657.  
17941859 H.S.Toogood, D.Leys, and N.S.Scrutton (2007).
Dynamics driving function: new insights from electron transferring flavoproteins and partner complexes.
  FEBS J, 274, 5481-5504.  
17580897 S.O.Mansoorabadi, C.J.Thibodeaux, and H.W.Liu (2007).
The diverse roles of flavin coenzymes--nature's most versatile thespians.
  J Org Chem, 72, 6329-6342.  
9585549 P.S.Brereton, M.F.Verhagen, Z.H.Zhou, and M.W.Adams (1998).
Effect of iron-sulfur cluster environment in modulating the thermodynamic properties and biological function of ferredoxin from Pyrococcus furiosus.
  Biochemistry, 37, 7351-7362.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.