title: Flavin radicals, conformational sampling and robust design principles in interprotein electron transfer: the trimethylamine dehydrogenase-electron-transferring flavoprotein complex.
abstract: TMADH (trimethylamine dehydrogenase) is a complex iron-sulphur flavoprotein that forms a soluble electron-transfer complex with ETF (electron-transferring flavoprotein). The mechanism of electron transfer between TMADH and ETF has been studied using stopped-flow kinetic and mutagenesis methods, and more recently by X-ray crystallography. Potentiometric methods have also been used to identify key residues involved in the stabilization of the flavin radical semiquinone species in ETF. These studies have demonstrated a key role for 'conformational sampling' in the electron-transfer complex, facilitated by two-site contact of ETF with TMADH. Exploration of three-dimensional space in the complex allows the FAD of ETF to find conformations compatible with enhanced electronic coupling with the 4Fe-4S centre of TMADH. This mechanism of electron transfer provides for a more robust and accessible design principle for interprotein electron transfer compared with simpler models that invoke the collision of redox partners followed by electron transfer. The structure of the TMADH-ETF complex confirms the role of key residues in electron transfer and molecular assembly, originally suggested from detailed kinetic studies in wild-type and mutant complexes, and from molecular modelling.
authors.affiliation: Department of Biochemistry, University of Leicester, University Road, Leicester LEI 7RH, UK.
authors.forename: David
authors.initials: D
authors.lastname: Leys
authors.forename: Jaswir
authors.initials: J
authors.lastname: Basran
authors.forename: François
authors.initials: F
authors.lastname: Talfournier
authors.forename: Kamaldeep K
authors.initials: KK
authors.lastname: Chohan
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Munro
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sutcliffe
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Scrutton
mesh_terms: D000818:Animals; D044927:Electron-Transferring Flavoproteins / Q000737:chemistry* / Q000378:metabolism; D004583:Electrons; D005415:Flavins; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary
chemical_list: D044927:Electron-Transferring Flavoproteins; D005415:Flavins; D005609:Free Radicals; D010089:Oxidoreductases, N-Demethylating; C023186:trimethylamine dehydrogenase