Disease relevance of FRDA

• Structure of fumarate reductase from Wolinella succinogenes at 2.2 A resolution [1].
• An essential sulfhydryl group at the substrate site of the fumarate reductase of Vibrio succinogenes [2].
• During growth with fumarate as the terminal electron transport acceptor and either formate or sulfide as the electron donor, Wolinella succinogenes induced a peri-plasmic protein (54 kDa) that reacted with an antiserum raised against the periplasmic fumarate reductase (Fcc) of Shewanella putrefaciens [3].

High impact information on FRDA

• Fumarate reductase couples the reduction of fumarate to succinate to the oxidation of quinol to quinone, in a reaction opposite to that catalysed by the related complex II of the respiratory chain (succinate dehydrogenase) [1].
• Essential role of Glu-C66 for menaquinol oxidation indicates transmembrane electrochemical potential generation by Wolinella succinogenes fumarate reductase [4].
• The structure of Wolinella succinogenes quinol: fumarate reductase and its relevance to the superfamily of succinate: quinone oxidoreductases [5].
• Mutation of the putative catalytic subunit of the enzyme resulted in a strain that lacked fumarate reductase activity and was unable to grow with fumarate as the terminal electron acceptor [6].
• The electron transport chain is made up of two dehydrogenases (hydrogenase and formate dehydrogenase) that catalyze the reduction of menaquinone, and fumarate reductase which catalyzes the oxidation of menaquinol [7].

Chemical compound and disease context of FRDA

• The fumarate reductase isolated from Wolinella succinogenes catalyzed succinate oxidation with quinones and fumarate reduction with the corresponding quinols at activities similar to those of the B. subtilis enzyme [8].
• Hydrogenase and fumarate reductase isolated from Wolinella succinogenes were incorporated into liposomes containing menaquinone [9].
• Reconciliation of apparently contradictory experimental results obtained on the quinol: fumarate reductase (QFR), a dihaem-containing respiratory membrane protein complex from Wolinella succinogenes, was previously obtained by the proposal of the so-called E-pathway hypothesis [10].
• Data from studies of mutant variants of the B. subtilis enzyme combined with available crystal structures of a similar enzyme, Wolinella succinogenes fumarate reductase, substantiate a proposed explanation for the mechanism of coupling between quinone reductase activity and transmembrane potential [11].
• (1) The fumarate reductase complex from Vibrio succinogenes contains one FAD molecule, one [4Fe-4S]3+(3+,2+) and one [2Fe-2S]2+(2+,1+) cluster per enzyme molecule [12].

Biological context of FRDA

• The genome contained genes encoding a heterotrimeric fumarate reductase, FrdCAB, with homology to the fumarate reductase of Wolinella succinogenes and the succinate dehydrogenase of Bacillus subtilis [6].
• The frdC2 gene located downstream of the fumarate reductase operon frdCAB possibly encodes a diheme cytochrome b that is similar to FrdC (41% identical residues) [13].
• As a consequence, the topology of the dicarboxylate binding site is much more similar to those of membrane-bound and soluble fumarate reductase enzymes from other organisms than to that found in the previous crystal forms of W. succinogenes QFR [14].
• Formate dehydrogenase and fumarate reductase are involved in the electron transport phosphorylation system of Vibrio succinogenes [15].

Anatomical context of FRDA

• 6. It is concluded that the substrate and the dye-reactive sites of formate dehydrogenase face the outside, while those of fumarate reductase face the inside of the cytoplasmic membrane of cells of V. succinogenes [15].

Associations of FRDA with chemical compounds

• Overall, acetate oxidation with fumarate proceeded through an open loop of citric acid cycle reactions, excluding succinate dehydrogenase, with fumarate reductase as the key reaction for electron delivery, whereas acetate oxidation in the syntrophic coculture required the complete citric acid cycle [16].
• Incorporation of formate dehydrogenase together with fumarate reductase and menaquinone resulted in proteoliposomes catalyzing the reduction of fumarate or DMN by formate [9].
• A W. succinogenes mutant (delta frdCAB) lacking the fumarate reductase operon did not grow with fumarate as terminal electron acceptor and either formate or sulfide as electron donor [13].
• The resulting mutants did not grow with formate and fumarate and did not contain fumarate reductase activity, FrdA or FrdC when grown with formate and nitrate [13].
• Methacrylate reduction by benzyl viologen radical was not catalyzed by fumarate reductase isolated from the membrane of W. succinogenes [17].

Other interactions of FRDA

• A periplasmic flavoprotein in Wolinella succinogenes that resembles the fumarate reductase of Shewanella putrefaciens [3].

Analytical, diagnostic and therapeutic context of FRDA

• Deletion and site-directed mutagenesis of the Wolinella succinogenes fumarate reductase operon [13].
• The structure of the dihaem cytochrome b of fumarate reductase in Wolinella succinogenes: circular dichroism and sequence analysis studies [18].

References