2GMH

Structure of Porcine Electron Transfer Flavoprotein-Ubiquinone Oxidoreductase in Complexed with Ubiquinone

Summary for 2GMH

• Entry DOI: 10.2210/pdb2gmh/pdb
• Related: 2GMJ
• Descriptor: Electron transfer flavoprotein-ubiquinone oxidoreductase, hexyl beta-D-galactopyranoside, SODIUM ION, ... (8 entities in total)
• Functional Keywords: electron-transfer, oxidoreductase, flavoprotein, ubiquinone
• Biological source: Sus scrofa (pig)
• Total number of polymer chains: 2
• Total formula weight: 134609.68

Authors

Zhang, J.,Frerman, F.E.,Kim, J.-J.P. (deposition date: 2006-04-06, release date: 2006-10-17, Last modification date: 2024-02-14)

Primary citation

Zhang, J.,Frerman, F.E.,Kim, J.J.
Structure of electron transfer flavoprotein-ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool.
Proc.Natl.Acad.Sci.Usa, 103:16212-16217, 2006

PubMed Abstract: 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.

PubMed: 17050691
DOI: 10.1073/pnas.0604567103

Experimental method

X-RAY DIFFRACTION (2.5 Å)