Succinate Dehydrogenase: Difference between revisions

<StructureSection load='2wdv' size='500' side='right' caption='Succinate dehydrogenase complex with FAD, protoporphrin, malate, Na+ ion, Fe2S2, Fe3S4, Fe4S4, [[2wdv]] ' scene=''>

[[Succinate Dehydrogenase]] (PDB = [[2wdv]] with empty ubiquinone binding site; PDB = [[1nek]] with ubiquinone bound), also called succinate-coenzyme Q reductase (SQR) or Complex II, is a tetrameric enzyme found in the cell membrane of some bacteria and the inner mitochondrial membrane of mammalian cells. It is classified as an α+β protein, as it contains <scene name='Michael_Vick_Sandbox_2/2wdv_sec_structure/1'>segregated regions</scene> of α helices and antiparallel β sheets. It is involved in two aspects of digestion; it catalyzes the oxidation of succinate to fumarate in the citric acid cycle by simultaneously reducing ubiquinone to ubiquinol in the electron transport chain <ref>PMID:14672929</ref>.

===Structure===

The tetramer is composed of <scene name='Michael_Vick_Sandbox_2/2wdv_hydrophob_and_polar/1'>two hydrophilic and two hydrophobic subunits</scene>. The hydrophilic subunits are named SdhA (PDB = [[2wdq]]) and SdhB; the former is a flavoprotein containing a covalently-bound FAD cofactor and a binding site for succinate, while the latter is a Fe-S protein bearing the three iron-sulfur clusters 2Fe-2S, 3Fe-4S, and 4Fe-4S. The hydrophobic subunits, termed SdhC and SdhD, anchor the protein in the mitochondrial membrane and formally comprise cytochrome b <ref>PMID:12966066</ref> <ref name="abc">PMID:12560550</ref>. This cytochrome contains six transmembrane α-helices, a heme b group, and a binding site for ubiquinone located in a space bounded by SdhB, SdhC, and SdhD <ref name="abc" /> <ref name="def">PMID:16407191</ref>.

===Binding sites===

====Succinate====

The binding site for succinate, in which the stereospecific dehydrogenation of succinate to fumarate is catalyzed, is located entirely on SdhA. <scene name='Michael_Vick_Sandbox_2/Suc_bind_site_and_fad/2'>Residues Thr254, His354, and Arg399</scene> stabilize the substrate with hydrogen bonding, while FAD removes the electrons and carries them to the first iron-sulfur cluster, 2Fe-2S, of SdhB <ref>PMID:235539</ref>. During this transfer, FAD is reduced to FADH2 <ref>Voet, Donald, Charlotte W. Pratt, and Judith G. Voet. Fundamentals of Biochemistry: Life at the Molecular Level. 2nd Ed. Hoboken, NJ: Wiley, 2008.</ref>. The Km for this reaction is approximately 10E(-3), while the Vmax is approximately 100 nmol/min/mg of protein <ref>PMID:2624174</ref>.

===Mechanisms===

====Succinate oxidation====

The exact mechanism for the oxidation of succinate to fumarate has not yet been elucidated. The initial deprotonation may be performed by FAD, Glu255, Arg286, or His242 of SdhA, and the following elimination may be a concerted E2 or E1cb elimination. In the concerted mechanism, the α-carbon is deprotonated by a base as FAD removes a hydride from the β-carbon; this is shown in image 1 <ref name="ghi">PMID:16950775</ref>.