Succinate Dehydrogenase: Difference between revisions

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Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michael Vick, David Canner, Michal Harel, Alexander Berchansky

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-'''Structure:'''
+===Structure:===
 The tetramer is composed of two hydrophilic and two hydrophobic subunits. The hydrophilic subunits are named SdhA and SdhB; the former is a flavoprotein containing a covalently-bound FAD cofactor a binding site for succinate, while the latter is 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> and <ref>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>PMID:12560550</ref> and <ref>PMID:16407191</ref>.
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 {{STRUCTURE_1nek |  PDB=1nek  |  SCENE=  }}
-'''Binding sites:'''
+===Binding sites:===
-''Succinate'' – The binding site for succinate, in which the stereospecific dehydrogenation of succinate to fumarate is catalyzed, is located entirely on SdhA. Residues Thr254, His354, and Arg399 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>ISBN:978-0-470-12930-2</ref>
+====Succinate====
+The binding site for succinate, in which the stereospecific dehydrogenation of succinate to fumarate is catalyzed, is located entirely on SdhA. Residues Thr254, His354, and Arg399 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>ISBN:978-0-470-12930-2</ref>
-''Ubiquinone'' – The binding site for ubiquinone, in which the substrate is reduced to ubiquinol, is bordered by subunits B, C, and D. Residues His207 of SdhB, Ser27 and Arg31 of SdhC, and Tyr83 of SdhD stabilize ubiquinone, while residues Pro160, Trp163, Trp164, and Ile209 of SdhB and Ser27 and Ile28 of SdhC provide the necessary hydrophobic environment that stabilizes the ring <ref>PMID:16407191</ref>.
+====Ubiquinone====
+The binding site for ubiquinone, in which the substrate is reduced to ubiquinol, is bordered by subunits B, C, and D. Residues His207 of SdhB, Ser27 and Arg31 of SdhC, and Tyr83 of SdhD stabilize ubiquinone, while residues Pro160, Trp163, Trp164, and Ile209 of SdhB and Ser27 and Ile28 of SdhC provide the necessary hydrophobic environment that stabilizes the ring <ref>PMID:16407191</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 [8].
+[[Image:S.D.Oxidation_of_Succinate_E2.gif]]
+Image 1: Oxidation of succinate to fumarate through E2 elimination
 <references/>