UniProt functional annotation for A0R2B1

UniProt code: A0R2B1.

Organism: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155).
Taxonomy: Bacteria; Actinobacteria; Actinobacteridae; Actinomycetales; Corynebacterineae; Mycobacteriaceae; Mycobacterium.
 
Function: Shows three enzymatic activities that share a first common step, the attack of thiamine-PP on 2-oxoglutarate (alpha- ketoglutarate, KG), leading to the formation of an enamine- thiamine-PP intermediate upon decarboxylation. Thus, displays KGD activity, catalyzing the decarboxylation from five-carbon 2- oxoglutarate to four-carbon succinate semialdehyde (SSA). Also catalyzes C-C bond formation between the activated aldehyde formed after decarboxylation of alpha-ketoglutarate and the carbonyl of glyoxylate (GLX), to yield 2-hydroxy-3-oxoadipate (HOA), which spontaneously decarboxylates to form 5-hydroxylevulinate (HLA). And is also a component of the 2-oxoglutarate dehydrogenase (ODH) complex, that catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2). The KG decarboxylase and KG dehydrogenase reactions provide two alternative, tightly regulated, pathways connecting the oxidative and reductive branches of the TCA cycle.
 
Catalytic activity: 2-oxoglutarate + glyoxylate = 2-hydroxy-3- oxoadipate + CO(2).
Catalytic activity: 2-oxoglutarate = succinate semialdehyde + CO(2).
Catalytic activity: 2-oxoglutarate + [dihydrolipoyllysine-residue succinyltransferase] lipoyllysine = [dihydrolipoyllysine-residue succinyltransferase] S-succinyldihydrolipoyllysine + CO(2).
Catalytic activity: Succinyl-CoA + enzyme N(6)- (dihydrolipoyl)lysine = CoA + enzyme N(6)-(S- succinyldihydrolipoyl)lysine.
Cofactor: Magnesium.
Cofactor: Thiamine pyrophosphate.
Enzyme regulation: Alpha-ketoglutarate dehydrogenase and decarboxylase activities are inhibited by unphosphorylated GarA, and allosterically activated by acetyl-CoA, the main substrate of the TCA cycle. Both the phosphoadenosine and acetyl moieties of acetyl-CoA are important for activation because neither CoA nor the synthetic compound S-(2-acetamidoethyl)-ethanethioate (which mimics the terminal acetyl-phosphopantetheine group of acetyl-CoA) has an activation effect.
Biophysicochemical properties: Kinetic parameters: KM=0.54 mM for alpha-ketoglutarate;
Pathway: Carbohydrate metabolism; tricarboxylic acid cycle; succinate from 2-oxoglutarate (transferase route): step 1/2.
Pathway: Carbohydrate metabolism; tricarboxylic acid cycle; succinyl-CoA from 2-oxoglutarate (dehydrogenase route): step 1/1.
Subunit: Homodimer. Interacts with the FHA domain of unphosphorylated GarA. The 2-oxoglutarate dehydrogenase (ODH) complex contains multiple copies of three enzymatic components: 2- oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3).
Domain: Is a fusion protein with two major domains exhibiting structural features of an E1 and E2 protein, and a short sequence stretch of E1 localized at the N-terminus, which is connected by a linker region to the rest of the protein (By similarity).
Disruption phenotype: Cells lacking this gene do not show any ODH activity, in contrast to wild-type, demonstrating that this protein is part of a functional ODH complex in mycobacteria.
Similarity: Belongs to the 2-oxoacid dehydrogenase family. Kgd subfamily.

Annotations taken from UniProtKB at the EBI.