InterPro domain: IPR001308

Electron transfer flavoproteins (ETFs) serve as specific electron acceptors for primary dehydrogenases, transferring the electrons to terminal respiratory systems. They can be functionally classified into constitutive, "housekeeping" ETFs, mainly involved in the oxidation of fatty acids (Group I), and ETFs produced by some prokaryotes under specific growth conditions, receiving electrons only from the oxidation of specific substrates (Group II) [ 1 ].

ETFs are heterodimeric proteins composed of an alpha and beta subunit, and contain an FAD cofactor and AMP [ 2 , 3 , 4 , 5 , 6 ]. ETF consists of three domains: domains I and II are formed by the N- and C-terminal portions of the alpha subunit, respectively, while domain III is formed by the beta subunit. Domains I and III share an almost identical alpha-beta-alpha sandwich fold, while domain II forms an alpha-beta-alpha sandwich similar to that of bacterial flavodoxins. FAD is bound in a cleft between domains II and III, while domain III binds the AMP molecule. Interactions between domains I and III stabilise the protein, forming a shallow bowl where domain II resides. The alpha subunit of both Group I and Group II ETFs is composed of domains I and II.

Many enterobacteria are able to convert carnitine, via crotonobetaine, to gamma-butyrobetaine in the presence of carbon and nitrogen sources under anaerobic conditions [ 7 ]. In Escherichia coli the enzymes involved in this pathway are encoded by the caiTABCDE operon [ 8 ]. The adjacent but divergent fixABCD operon also appears to be necessary for carnintine meatbolism [ 9 ]. The Fix proteins are homologous to proteins found in known electron transport pathways.

This entry includes electron transfer flavoprotein alpha subunit and the FixB protein.

1. Bradyrhizobium japonicum possesses two discrete sets of electron transfer flavoprotein genes: fixA, fixB and etfS, etfL. Arch. Microbiol. 165, 169-78
2. Biosynthesis, molecular cloning and sequencing of electron transfer flavoprotein. Prog. Clin. Biol. Res. 321, 637-52
3. Phylogenetic characterization of the ubiquitous electron transfer flavoprotein families ETF-alpha and ETF-beta. Res. Microbiol. 146, 397-404
4. Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution. Proc. Natl. Acad. Sci. U.S.A. 93, 14355-60
5. Crystal structure of Paracoccus denitrificans electron transfer flavoprotein: structural and electrostatic analysis of a conserved flavin binding domain. Biochemistry 38, 1977-89
6. Extensive conformational sampling in a ternary electron transfer complex. Nat. Struct. Biol. 10, 219-25
7. Bacterial carnitine metabolism. FEMS Microbiol. Lett. 147, 1-9
8. Molecular characterization of the cai operon necessary for carnitine metabolism in Escherichia coli. Mol. Microbiol. 13, 775-86
9. The fixA and fixB genes are necessary for anaerobic carnitine reduction in Escherichia coli. J. Bacteriol. 184, 4044-7