2-Oxoglutarate Dehydrogenase
From Proteopedia
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| - | <StructureSection load='2jgd' size='400' side='right' scene=' | + | <StructureSection load='2jgd' size='400' side='right' scene='' caption='Dimer of E. coli 2-oxogluterate dehydrogenase E1 component complex with AMP (stick model), [[2jgd]]'> |
'''2-oxoglutarate dehydrogenase''' is a complex of three components: E1, E2 and E3. The enzyme '''2-Oxoglutarate Dehydrogenase E1o''' (OGDH) is a subunit the 2-Oxoglutarate Dehydrogenase ([[EC Number]] [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.2 1.2.4.2]) multi enzyme complex. This subunit is a homo-dimer and one of three enzymes that make up the multi-enzyme complex of 2-Oxoglutarate Dehydrogenase. Each of the <scene name='Lucas_Evans_Sandbox/Monomer/2'>monomers</scene> that make up the homo-dimer have an <scene name='Lucas_Evans_Sandbox/Amp1/1'>adenosine monophosphate</scene> cofactor that facilitates the catalysis. E1o is not categorized in the Structural Classification of Proteins (SCOP); however, the <scene name='Lucas_Evans_Sandbox/Secondary_structure/2'>secondary structure</scene> of one of the dimers shows that this enzyme has large sections of alpha-helices followed by a large sections of parallel beta-pleated sheets these alpha and beta subunits are fused as a single polypeptide <ref name="one">PMID:17367808 </ref>. E2 component is '''dihydrolipoyl succinyltransferase''' or '''dihydrolipoamide succinyltransferase''' (DLST) with lipoic acid as coenzyme and E3 is [[Dihydrolipoamide dehydrogenase]] (DLD) with FAD as coenzyme. The 2-oxoglutaqrate dehydrogenase complex participates in then citric acid cycle, lysine degradation and tryptophan metabolism. See also [[Krebs cycle step 4]]. | '''2-oxoglutarate dehydrogenase''' is a complex of three components: E1, E2 and E3. The enzyme '''2-Oxoglutarate Dehydrogenase E1o''' (OGDH) is a subunit the 2-Oxoglutarate Dehydrogenase ([[EC Number]] [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.4.2 1.2.4.2]) multi enzyme complex. This subunit is a homo-dimer and one of three enzymes that make up the multi-enzyme complex of 2-Oxoglutarate Dehydrogenase. Each of the <scene name='Lucas_Evans_Sandbox/Monomer/2'>monomers</scene> that make up the homo-dimer have an <scene name='Lucas_Evans_Sandbox/Amp1/1'>adenosine monophosphate</scene> cofactor that facilitates the catalysis. E1o is not categorized in the Structural Classification of Proteins (SCOP); however, the <scene name='Lucas_Evans_Sandbox/Secondary_structure/2'>secondary structure</scene> of one of the dimers shows that this enzyme has large sections of alpha-helices followed by a large sections of parallel beta-pleated sheets these alpha and beta subunits are fused as a single polypeptide <ref name="one">PMID:17367808 </ref>. E2 component is '''dihydrolipoyl succinyltransferase''' or '''dihydrolipoamide succinyltransferase''' (DLST) with lipoic acid as coenzyme and E3 is [[Dihydrolipoamide dehydrogenase]] (DLD) with FAD as coenzyme. The 2-oxoglutaqrate dehydrogenase complex participates in then citric acid cycle, lysine degradation and tryptophan metabolism. See also [[Krebs cycle step 4]]. | ||
__TOC__ | __TOC__ | ||
==Catalysis== | ==Catalysis== | ||
| - | [[Image:oxoglutarate dehydrogenase.png|thumb|left| | + | [[Image:oxoglutarate dehydrogenase.png|thumb|left|300px|The complete reaction of the Oxoglutarate Dehydrogenase Multi-Enzyme Complex]] |
| + | {{Clear}} | ||
| + | E1o catalyzes the oxidative decarboxylation of alpha-ketoglutarate to Succinyl-CoA at its <scene name='Lucas_Evans_Sandbox/Active_site/1'>active site</scene> in the fourth step of the metabolic citric acid cycle by acting as a base to facilitate the decarboxylation <ref name="one" />. The main residues responsible for the catalysis are thought to be His 260, Phe 227, Gln685, His 729, Ser302, and His 298 <ref name="one" />. E1o is also thought to have a single active site. E1o also requrires two cofactors in order for it to function properly, Thiamine diphosphate and divalent magnesium ion if either are not present then the enzyme has nearly no activity<ref name="two">PMID:192200 </ref>. The specific mexhanism of the E1o subunit are currently unknown; however, There are several theories as to how it functions, among them is the Hexa Uni Ping Pong theory<ref name="two" />. Even though the mechanism isn't fully know the kinetic data have be calculated and are as follows: | ||
* KM: 0.14 ± 0.04 mM | * KM: 0.14 ± 0.04 mM | ||
* Vmax : 9 ± 3 μmol.min-1.mg-1<ref name="three" >PMID:17657817</ref> | * Vmax : 9 ± 3 μmol.min-1.mg-1<ref name="three" >PMID:17657817</ref> | ||
Revision as of 15:40, 13 May 2015
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3D structures of 2-Oxoglutarate dehydrogenase
Updated on 13-May-2015
References
- ↑ 1.0 1.1 1.2 1.3 Frank RA, Price AJ, Northrop FD, Perham RN, Luisi BF. Crystal structure of the E1 component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex. J Mol Biol. 2007 May 4;368(3):639-51. Epub 2007 Feb 7. PMID:17367808 doi:10.1016/j.jmb.2007.01.080
- ↑ 2.0 2.1 McMinn CL, Ottaway JH. Studies on the mechanism and kinetics of the 2-oxoglutarate dehydrogenase system from pig heart. Biochem J. 1977 Mar 1;161(3):569-81. PMID:192200
- ↑ Leung PS, Rossaro L, Davis PA, Park O, Tanaka A, Kikuchi K, Miyakawa H, Norman GL, Lee W, Gershwin ME. Antimitochondrial antibodies in acute liver failure: implications for primary biliary cirrhosis. Hepatology. 2007 Nov;46(5):1436-42. PMID:17657817 doi:10.1002/hep.21828
- ↑ Voet, Donald, Judith G. Voet, and Charlotte W. Pratt. Fundamentals of Biochemistry: Life at the Molecular Level. Hoboken, NJ: Wiley, 2008. p.580
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