Disease relevance of SDHD

• The smallest membrane-anchoring subunit (QPs3) of bovine heart succinate:ubiquinone reductase was overexpressed in Escherichia coli JM109 as a glutathione S-transferase fusion protein using the expression vector pGEX2T/QPs3 [1].

High impact information on SDHD

• The recombinant QPs3 binds ubiquinone, causing a spectral blue shift [1].
• Histidine residues at positions 46 and 60 are responsible for heme ligation because the H46N- or H60N-substituted QPs3 fail to restore cytochrome b560 upon addition of hemin chloride [1].
• Identification of quinone-binding and heme-ligating residues of the smallest membrane-anchoring subunit (QPs3) of bovine heart mitochondrial succinate:ubiquinone reductase [1].
• Two amino acid residues, serine 33 and tyrosine 37, in the putative ubiquinone binding domain of QPs3 are involved in ubiquinone binding because the S33A- or Y37A-substituted recombinant QPs3s do not cause the spectral blue shift of ubiquinone [1].
• The molecular mass of QPs3, deduced from the nucleotide sequence, is 10,989 Da [2].

Biological context of SDHD

• QPs3 is a very hydrophobic protein; the hydropathy plot of the amino acid sequence reveals three transmembrane helices [2].
• This cDNA is 1330 base pairs long with an open reading frame of 474 base pairs that encodes the 103 amino acid residues of mature QPs3 and a 55-amino acid residue presequence [2].
• SDHC and SDHD are the first tumor suppressor genes of mitochondrial proteins [3].

Associations of SDHD with chemical compounds

• The ubiquinone-binding domain in the proposed model of QPs3 is probably located at the end of transmembrane helix 1 toward the C-side of the mitochondrial inner membrane [2].
• Although recombinant QPs3 contains little cytochrome b560 heme, the spectral characteristics of cytochrome b560 are reconstituted upon addition of hemin chloride [1].
• CII-1 and CII-2 are the flavoprotein and iron-sulfur protein, respectively, of succinate dehydrogenase; CII-3 and CII-4 have not been functionally indentified [4].

Analytical, diagnostic and therapeutic context of SDHD

• Upon titration of the recombinant protein with ubiquinone, a saturation behavior is observed, suggesting that the binding is specific and that recombinant QPs3 may be in the functionally active state [1].

References