TCDB is operated by the Saier Lab Bioinformatics Group

3.D.10 The Prokaryotic Succinate Dehydrogenase (SDH) Family

The succinate oxidase and succinate:menaquinone reductase activities are lost when the transmembrane electrochemical proton potential (pmf) is abolished by rupture of the bacteria or addition of a protonophore. It had been proposed that the endergonic reduction of menaquinone by succinate is driven by the electrochemical proton potential. Opposite sides of the cytoplasmic membrane were envisaged to be separately involved in the binding of protons upon the reduction of menaquinone and their release upon succinate oxidation, with the two reactions linked by the transfer of two electrons through the enzyme. However, it has also been argued that the observed pmf dependence is not associated specifically with the succinate:menaquinone reductase.

Madej et al. (2006) described the purification, reconstitution into proteoliposomes, and functional characterization of the diheme-containing succinate:menaquinone reductase from B. licheniformis, and, with the help of the design, synthesis, and characterization of quinones with finely tuned oxidation/reduction potentials, provided evidence for the pmf-dependent catalysis of succinate oxidation by quinone as well as for pmf generation upon catalysis of fumarate reduction by quinol (see also Simon et al., 2008).

Membrane protein complexes can support both the generation and utilisation of a transmembrane electrochemical proton potential (Deltap), either by supporting transmembrane electron transfer coupled to protolytic reactions on opposite sides of the membrane or by supporting transmembrane proton transfer. The first mechanism has been demonstrated for the pmf-dependent catalysis of succinate oxidation by quinone in the case of the dihaem-containing succinate:menaquinone reductase (SQR) from the Gram-positive bacterium Bacillus licheniformis. This is physiologically relevant in that it allows the transmembrane potential to drive the endergonic oxidation of succinate by menaquinone by the dihaem-containing SQR of Gram-positive bacteria. A related but different respiratory membrane protein complex is the dihaem- containing quinol:fumarate reductase (QFR) of the ε-proteobacterium Wolinella succinogenes. For this enzyme, evidence has been obtained that both mechanisms are combined, so as to facilitate transmembrane electron transfer by proton transfer via an essential compensatory transmembrane proton transfer pathway ('E-pathway'). Although the reduction of fumarate by menaquinol is exergonic, it is not exergonic enough to support the generation of a pmf. This compensatory 'E-pathway' appears to be required by all dihaem-containing QFR enzymes and results in the overall reaction being electroneutral. However, Madej et al. 2009 showed that the reverse reaction, the oxidation of succinate by quinone, as catalysed by the W. succinogenes QFR, is electrogenic.

The di-heme family of succinate:quinone oxidoreductases support electron transfer across the biological membranes in which they are embedded (Lancaster 2013). In the case of the di-heme-containing succinate:menaquinone reductase (SQR) from Gram-positive bacteria and other menaquinone-containing bacteria, this results in an electrogenic reaction. This is physiologically relevant in that it allows the transmembrane electrochemical proton potential Δp to drive the endergonic oxidation of succinate by menaquinone. In the case of the reverse reaction, menaquinol oxidation by fumarate, catalysed by the di-heme-containing quinol:fumarate reductase (QFR), this electrogenic electron transfer reaction is compensated by proton transfer via an essential transmembrane proton transfer pathway ('E-pathway'). Although the reduction of fumarate by menaquinol is exergonic, it is not sufficiently exergonic to support the generation of a Δp. This compensatory 'E-pathway' appears to be required by all di-heme-containing QFR enzymes and results in the overall reaction being electroneutral (Lancaster 2013). Other members of this diverse family  and the crystal structure of the QFR from the anaerobic Wolinella succinogenes at 1.78Å resolution have been reviewed (Lancaster 2013).

The generalized reaction catalyzed by these bacterial SDHs may be:

succinate (in) + menaquinone (membrane) + 2H+ (out) ⇌ fumarate (in) + menaquinol (membrane) + 2H+ (in)

References associated with 3.D.10 family:

Hamann, N., E. Bill, J.E. Shokes, R.A. Scott, M. Bennati, and R. Hedderich. (2009). The CCG-domain-containing subunit SdhE of succinate:quinone oxidoreductase from Sulfolobus solfataricus P2 binds a [4Fe-4S] cluster. J Biol Inorg Chem 14: 457-470. 19085017
Lancaster, C.R. (2013). The di-heme family of respiratory complex II enzymes. Biochim. Biophys. Acta. 1827: 679-687. 23466335
Lancaster, C.R., E. Herzog, H.D. Juhnke, M.G. Madej, F.G. Müller, R. Paul, and P.G. Schleidt. (2008). Electroneutral and electrogenic catalysis by dihaem-containing succinate:quinone oxidoreductases. Biochem Soc Trans 36: 996-1000. 18793177
Madej, M.G., F.G. Müller, J. Ploch, and C.R. Lancaster. (2009). Limited reversibility of transmembrane proton transfer assisting transmembrane electron transfer in a dihaem-containing succinate:quinone oxidoreductase. Biochim. Biophys. Acta. 1787: 593-600. 19254686
Madej, M.G., H.R. Nasiri, N.S. Hilgendorff, H. Schwalbe, and C.R. Lancaster. (2006). Evidence for transmembrane proton transfer in a dihaem-containing membrane protein complex. EMBO. J. 25: 4963-4970. 17024183
Madej, M.G., H.R. Nasiri, N.S. Hilgendorff, H. Schwalbe, G. Unden, and C.R. Lancaster. (2006). Experimental evidence for proton motive force-dependent catalysis by the diheme-containing succinate:menaquinone oxidoreductase from the Gram-positive bacterium Bacillus licheniformis. Biochemistry 45: 15049-15055. 17154542
Simon, J., R.J. van Spanning, and D.J. Richardson. (2008). The organisation of proton motive and non-proton motive redox loops in prokaryotic respiratory systems. Biochim. Biophys. Acta. 1777: 1480-1490. 18930017
Xin, Y., Y.K. Lu, R. Fromme, P. Fromme, and R.E. Blankenship. (2009). Purification, characterization and crystallization of menaquinol:fumarate oxidoreductase from the green filamentous photosynthetic bacterium Chloroflexus aurantiacus. Biochim. Biophys. Acta. 1787: 86-96. 19103151