|Gene:||sucA||Accession Numbers: EG10979 (EcoCyc), b0726, ECK0714|
Synonyms: lys, lys+met, E1(o) subunit
Component of: 2-oxoglutarate dehydrogenase complex (summary available)
Subunit composition of
2-oxoglutarate decarboxylase, thiamine-requiring = [SucA]12
subunit of E1(0) component of 2-oxoglutarate dehydrogenase = SucA
E. coli SucA is responsible for the 2-oxoglutarate decarboxylase activity of the 2-oxoglutarate dehydrogenase multienzyme complex (OGDHC) that catalyzes the conversion of 2-oxoglutarate (2-ketoglutarate) to succinyl-CoA and CO2, with the production of NADH (see 2-oxoglutarate decarboxylation to succinyl-CoA).
The OGDHC is a member of the 2-oxo acid dehydrogenase family [Bunik08]. Members of this family contain multiple copies of three enzymatic components: 2-oxoglutarate decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3). In most Gram-positive bacteria and in mitochondria the E1 component is a heterodimer composed of two subunits, while in most (but not all) Gram-negative bacteria it is made up of a single type of subunit. In both cases multiple copies of the E1 component along with multiple copies of the E3 component are assembled around an E2 core of 24 subunits with octahedral symmetry, or 60 subunits with eicosahedral symmetry (depending on which complex and species) [Reed01]. In E. coli the E3 component is shared with the pyruvate dehydrogenase and glycine cleavage multi-enzyme complexes. E1 and E2 differ slightly for the 2-oxoglutarate and pyruvate dehydrogenase complexes, and are designated (o) and (p) to distinguish them.
The E. coli OGDHC contains 12 units of the E1(o) component 2-oxoglutarate decarboxylase, thiamine-requiring encoded by sucA, 24 units of the E2(o) comoponent dihydrolipoyltranssuccinylase encoded by sucB, and 2 units of the E3 component lipoamide dehydrogenase encoded by lpd. The 24 E2(o) units form the octahedral core of the complex. They contain lipoyllysine and binding sites for dimers of the E1(o) and E3 subunits. Electron cryotomography showed that they are flexibly tethered to the E2 core [Murphy05].
During the OGDHC reaction cycle, 2-oxoglutarate is bound and decarboxylated by SucA, a thiamin-diphosphate cofactor containing enzyme. The crystal structure of a truncated, apo form of SucA lacking the N-terminal 77 residues has been determined at 2.6 Å resolution. The structure of the holo form with thiamin diphoisphate and Mg2+ was determined at 3.5 Å resolution. The truncated form retained decarboxylase activity but did not assemble with E2(o) into an OGDH complex. Data also suggested the presence of an AMP binding site [Frank07]. An oxygen-dependent thiamin free radical was demonstrated in the OGDHC, which was generated by a side reaction with O2 [Frank08].
Studies of engineered SucA prepared by saturation mutagenesis of His260 and His298 suggested that His260 is required for substrate recognition, but His298 could be replaced by hydrophobic residues of similar size. Data also suggested that E2(o) has a role in specificity [Shim11].
REACTION: E1(o) + TPP = E1(o).TPP, E1(o).TPP + 2-oxoglutarate = E1(o).hydroxycarboxypropylTPP + CO(2), E1(o).hydroxycarboxypropylTPP + E2(o).lipoate(S2) = E1(o).TPP + E2(o).lipoate(SH)(S-succinyl) (see [Waskiewicz84, Steginsky85])
The sucA gene was cloned and sequenced in earlier work [Spencer82, Darlison84] and regulation of sucABCD was studied [Park97, Cunningham98a]. The sucAB and sucCD genes were shown to be mutually essential, with either pair sufficient to produce succinyl-CoA, but simultaneous deletion of sucAB and sucCD was not viable [Yu06].
|Map Position: [757,929 -> 760,730] (16.34 centisomes)||Length: 2802 bp / 933 aa|
Molecular Weight of Polypeptide: 105.06 kD (from nucleotide sequence)
Unification Links: ASAP:ABE-0002478 , CGSC:146 , DIP:DIP-36225N , EchoBASE:EB0972 , EcoGene:EG10979 , EcoliWiki:b0726 , Mint:MINT-1243484 , ModBase:P0AFG3 , OU-Microarray:b0726 , PortEco:sucA , PR:PRO_000024002 , Pride:P0AFG3 , Protein Model Portal:P0AFG3 , RefSeq:NP_415254 , RegulonDB:EG10979 , SMR:P0AFG3 , String:511145.b0726 , UniProt:P0AFG3
Relationship Links: InterPro:IN-FAMILY:IPR001017 , InterPro:IN-FAMILY:IPR005475 , InterPro:IN-FAMILY:IPR011603 , Panther:IN-FAMILY:PTHR23152 , PDB:Structure:2JGD , Pfam:IN-FAMILY:PF00676 , Pfam:IN-FAMILY:PF02779 , Smart:IN-FAMILY:SM00861
|Biological Process:||GO:0006096 - glycolytic process
GO:0006099 - tricarboxylic acid cycle [GOA01a]
GO:0008152 - metabolic process [GOA01a]
GO:0055114 - oxidation-reduction process [UniProtGOA11a]
|Molecular Function:||GO:0000287 - magnesium ion binding
GO:0004591 - oxoglutarate dehydrogenase (succinyl-transferring) activity [GOA01, GOA01a, Frank07]
GO:0005515 - protein binding [Rajagopala14, Butland05]
GO:0030976 - thiamine pyrophosphate binding [GOA01a, Frank07]
GO:0042802 - identical protein binding [Rajagopala14, Lasserre06]
GO:0016491 - oxidoreductase activity [UniProtGOA11a]
GO:0016624 - oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor [GOA01a]
|Cellular Component:||GO:0005829 - cytosol [DiazMejia09, Ishihama08, Lasserre06]|
|MultiFun Terms:||metabolism → energy metabolism, carbon → TCA cycle|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB Lennox||Yes||37||Aerobic||7||Yes [Baba06, Comment 1]|
|M9 medium with 1% glycerol||Yes||37||Aerobic||7.2||0.35||Yes [Joyce06, Comment 2]|
|MOPS medium with 0.4% glucose||Yes||37||Aerobic||7.2||0.22||Yes [Baba06, Comment 1] |
Yes [Feist07, Comment 3]
Enzymatic reaction of: 2-oxoglutarate decarboxylase
Synonyms: oxoglutarate oxidoreductase, decarboxylase, 2-ketoglutarate decarboxylase
EC Number: 18.104.22.168
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.
The reaction is physiologically favored in the direction shown.
In Pathways: 2-oxoglutarate decarboxylation to succinyl-CoA
E1(o) activity was analyzed by mixing purified E1(o) enzyme with E2(o) and E3 enzymes in vitro and monitoring the formation of NADH spectrophotometrically [Frank07]. The [Waskiewicz84] data are for E. coli B.
Subunit of: 2-oxoglutarate dehydrogenase complex
Subunit composition of
2-oxoglutarate dehydrogenase complex = [(SucA)12][(SucB)24][(Lpd)2]
2-oxoglutarate decarboxylase, thiamine-requiring = (SucA)12 (extended summary available)
subunit of E1(0) component of 2-oxoglutarate dehydrogenase = SucA
dihydrolipoyltranssuccinylase = (SucB)24 (extended summary available)
lipoamide dehydrogenase = (Lpd)2 (extended summary available)
E3 monomer = Lpd
The 2-oxoglutarate (2-ketoglutarate) dehydrogenase complex is similar in enzyme composition and complex reactions to the pyruvate dehydrogenase complex reactions [Perham87, Stephens83, Perham89] (see 2-oxoglutarate decarboxylation to succinyl-CoA and pyruvate decarboxylation to acetyl CoA).
SUBREACTIONS: E1(o) + TPP = E1(o).TPP E1(o).TPP + succinate = E1(o).hydroxycarboxypropylTPP + CO(2) E1(o).hydroxycarboxypropylTPP + E2(o).lipoate(S2) = E1(o).TPP + E2(o).lipoate(SH)(S-succinyl) E2(o).lipoate(SH)(S-succinyl) + CoA = E2(o).lip(SH)2 + succinylCoA E3 + FAD = E3.FAD E3.FAD + E2(o).lip(SH)2 = E3.FADH(2) + E2(o).lip(S)2 E3.FADH(2) + NAD(+) = E3.FAD + NADH + H(+) (see [Steginsky85, Waskiewicz84].
Enzymatic reaction of: 2-oxoglutarate dehydrogenase
Synonyms: α-ketoglutarate dehydrogenase, 2-ketoglutarate dehydrogenase
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
The reaction is favored in the direction shown.
In Pathways: 2-oxoglutarate decarboxylation to succinyl-CoA , superpathway of glycolysis, pyruvate dehydrogenase, TCA, and glyoxylate bypass , superpathway of glyoxylate bypass and TCA , TCA cycle I (prokaryotic)
The [Waskiewicz84] data are for E. coli B.
10/20/97 Gene b0726 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10979; confirmed by SwissProt match.
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Gupta79: Gupta SC, Dekker EE (1979). "Oxidation of 2-keto-4-hydroxyglutarate by pig heart and Escherichia coli alpha-ketoglutarate dehydrogenase complex." Arch Biochem Biophys 192(1);324-6. PMID: 373631
Gupta80: Gupta SC, Dekker EE (1980). "Evidence for the identity and some comparative properties of alpha-ketoglutarate and 2-keto-4-hydroxyglutarate dehydrogenase activity." J Biol Chem 255(3);1107-12. PMID: 6985904
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Pettit73: Pettit FH, Hamilton L, Munk P, Namihira G, Eley MH, Willms CR, Reed LJ (1973). "Alpha-keto acid dehydrogenase complexes. XIX. Subunit structure of the Escherichia coli alpha-ketoglutarate dehydrogenase complex." J Biol Chem 248(15);5282-90. PMID: 4588679
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