Q73WX4 · KGD_MYCPA
- ProteinMultifunctional 2-oxoglutarate metabolism enzyme
- Genekgd
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1247 (go to sequence)
- Protein existenceInferred from homology
- Annotation score5/5
Function
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 CO2. The KG decarboxylase and KG dehydrogenase reactions provide two alternative, tightly regulated, pathways connecting the oxidative and reductive branches of the TCA cycle (By similarity).
Catalytic activity
- 2-oxoglutarate + glyoxylate + H+ = 2-hydroxy-3-oxoadipate + CO2
Cofactor
Protein has several cofactor binding sites:
Activity 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.
Pathway
Carbohydrate metabolism; tricarboxylic acid cycle; succinate from 2-oxoglutarate (transferase route): step 1/2.
Carbohydrate metabolism; tricarboxylic acid cycle; succinyl-CoA from 2-oxoglutarate (dehydrogenase route): step 1/1.
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 332 | Proton acceptor; for succinyltransferase activity | ||||
Sequence: H | ||||||
Binding site | 558 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 597 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 622 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 622 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 624 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 665 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 665 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 666 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 667 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 698 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 698 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 700 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 1040 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 1058 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: T | ||||||
Binding site | 1074 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: R | ||||||
Binding site | 1109 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: K | ||||||
Binding site | 1112 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: S | ||||||
Binding site | 1162 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: Q | ||||||
Binding site | 1169 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: R | ||||||
Binding site | 1170 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: R |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | 2-hydroxy-3-oxoadipate synthase activity | |
Molecular Function | 2-oxoglutarate decarboxylase activity | |
Molecular Function | dihydrolipoyllysine-residue succinyltransferase activity | |
Molecular Function | magnesium ion binding | |
Molecular Function | oxoglutarate dehydrogenase (succinyl-transferring) activity | |
Molecular Function | thiamine pyrophosphate binding | |
Biological Process | tricarboxylic acid cycle |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMultifunctional 2-oxoglutarate metabolism enzyme
- Alternative names
Including 2 domains:
- Recommended name2-oxoglutarate dehydrogenase E1 component
- EC number
- Short namesODH E1 component
- Alternative names
- Recommended nameDihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageBacteria > Actinomycetota > Actinomycetes > Mycobacteriales > Mycobacteriaceae > Mycobacterium > Mycobacterium avium complex (MAC)
Accessions
- Primary accessionQ73WX4
Proteomes
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000310717 | 1-1247 | Multifunctional 2-oxoglutarate metabolism enzyme | |||
Sequence: MSNISSPFGQNEWLVEEMYRKFRDDPSSVDPSWHEFLVDYNPEPTGDSVLAAPASTDGPSAPAPAAPQTAQPALPAQTAPPAQTAQPARPAPQPAAAPGNGASTRPAKPATPPPAEGDELQTLRGAAAAVVKNMSASLEVPTATSVRAIPAKLLIDNRIVINNQLKRTRGGKISFTHLLGYALVQAIKKFPNMNRHYAEIDGKPTAITPAHTNLGLAIDLQGKDGKRSLVVAGIKNCETMRFAQFVTAYEDIVRRARDGKLTAEDFAGVTISLTNPGTIGTVHSVPRLMNGQGAIIGVGAMEYPAEFQGASEERIAELGIGKLITLTSTYDHRIIQGAESGDFLRTIHEMLLSDGFWDDIFRELSIPYLPIRWSTDNPDSIVDKNARVMELIAAYRNRGHLMADIDPLRLDGSRFRSHPDLEILNHGLTLWDLDRVFKVNGFAGAEYKKLRDILGLLRDAYCRHIGVEYTHILDPEQQEWLQQRVETKHVKPTVAEQKFILSKLNAAEAFETFLQTKYVGQKRFSLEGAESVIPMMDAAIDQCAEHGLDEVVIGMPHRGRLNVLANIVGKPYSQIFSEFEGNLNPAQAHGSGDVKYHLGATGVYLQMFGDNDIQVSLTANPSHLEAVDPVLEGLVRAKQDLLDHGADDQGDEKAFSVVPMMLHGDAAFAGQGVVAETLNLTHLPGYRVGGTIHIIVNNQIGFTTAPEHSRSSEYCTDVAKMIGAPIFHVNGDDPEACAWVAKLAVDFRQKFKKDVVIDMLCYRKRGHNEGDDPSMTNPAMYDVVDIKRGVRKSYTEALIGRGDISMKEAEDALRDYQGQLERVFNEVRELEKHGVGPSESVEADQMLPAGLATAVDKALLARIGDAFLALPEGFTAHPRVQPVLEKRREMAYEGKIDWAFAELLALGSLVAGGKLVRLSGQDTRRGTFSQRHSVIIDRNTGEEFTPLQLLATNPDGTPTGGKFLVYDSPLSEYAAVGFEYGYTVGNPDALVLWEAQFGDFVNGAQSIIDEFISSGEAKWGQLSNVVLLLPHGHEGQGPDHTSARIERFLQLWAEGSMTIAMPSTPSNYFHLLRRHALDGIKRPLIVFTPKSMLRNKAAVSDIKDFTEIKFRSVLEEPTYEDGIGDRGKVSRVLLTSGKLYYELVARKNKDNRDDVAIVRIEQLAPLPKRRLGETLDRYPNVREYFWVQEEPANQGAWPRFGLELPELLPDKLTGLKRISRRAMSAPSSGSSKVHAVEQQEIIDTAFA |
Interaction
Subunit
Homodimer. The 2-oxoglutarate dehydrogenase (ODH) complex contains multiple copies of three enzymatic components: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-41 | 2-oxoglutarate dehydrogenase E1, N-terminal part | ||||
Sequence: MSNISSPFGQNEWLVEEMYRKFRDDPSSVDPSWHEFLVDYN | ||||||
Region | 23-118 | Disordered | ||||
Sequence: RDDPSSVDPSWHEFLVDYNPEPTGDSVLAAPASTDGPSAPAPAAPQTAQPALPAQTAPPAQTAQPARPAPQPAAAPGNGASTRPAKPATPPPAEGD | ||||||
Region | 42-104 | Linker | ||||
Sequence: PEPTGDSVLAAPASTDGPSAPAPAAPQTAQPALPAQTAPPAQTAQPARPAPQPAAAPGNGAST | ||||||
Region | 105-353 | Succinyltransferase E2 | ||||
Sequence: RPAKPATPPPAEGDELQTLRGAAAAVVKNMSASLEVPTATSVRAIPAKLLIDNRIVINNQLKRTRGGKISFTHLLGYALVQAIKKFPNMNRHYAEIDGKPTAITPAHTNLGLAIDLQGKDGKRSLVVAGIKNCETMRFAQFVTAYEDIVRRARDGKLTAEDFAGVTISLTNPGTIGTVHSVPRLMNGQGAIIGVGAMEYPAEFQGASEERIAELGIGKLITLTSTYDHRIIQGAESGDFLRTIHEMLLS | ||||||
Region | 354-1247 | 2-oxoglutarate dehydrogenase E1, C-terminal part | ||||
Sequence: DGFWDDIFRELSIPYLPIRWSTDNPDSIVDKNARVMELIAAYRNRGHLMADIDPLRLDGSRFRSHPDLEILNHGLTLWDLDRVFKVNGFAGAEYKKLRDILGLLRDAYCRHIGVEYTHILDPEQQEWLQQRVETKHVKPTVAEQKFILSKLNAAEAFETFLQTKYVGQKRFSLEGAESVIPMMDAAIDQCAEHGLDEVVIGMPHRGRLNVLANIVGKPYSQIFSEFEGNLNPAQAHGSGDVKYHLGATGVYLQMFGDNDIQVSLTANPSHLEAVDPVLEGLVRAKQDLLDHGADDQGDEKAFSVVPMMLHGDAAFAGQGVVAETLNLTHLPGYRVGGTIHIIVNNQIGFTTAPEHSRSSEYCTDVAKMIGAPIFHVNGDDPEACAWVAKLAVDFRQKFKKDVVIDMLCYRKRGHNEGDDPSMTNPAMYDVVDIKRGVRKSYTEALIGRGDISMKEAEDALRDYQGQLERVFNEVRELEKHGVGPSESVEADQMLPAGLATAVDKALLARIGDAFLALPEGFTAHPRVQPVLEKRREMAYEGKIDWAFAELLALGSLVAGGKLVRLSGQDTRRGTFSQRHSVIIDRNTGEEFTPLQLLATNPDGTPTGGKFLVYDSPLSEYAAVGFEYGYTVGNPDALVLWEAQFGDFVNGAQSIIDEFISSGEAKWGQLSNVVLLLPHGHEGQGPDHTSARIERFLQLWAEGSMTIAMPSTPSNYFHLLRRHALDGIKRPLIVFTPKSMLRNKAAVSDIKDFTEIKFRSVLEEPTYEDGIGDRGKVSRVLLTSGKLYYELVARKNKDNRDDVAIVRIEQLAPLPKRRLGETLDRYPNVREYFWVQEEPANQGAWPRFGLELPELLPDKLTGLKRISRRAMSAPSSGSSKVHAVEQQEIIDTAFA | ||||||
Coiled coil | 803-833 | |||||
Sequence: DISMKEAEDALRDYQGQLERVFNEVRELEKH |
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.
Sequence similarities
Belongs to the 2-oxoacid dehydrogenase family. Kgd subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,247
- Mass (Da)137,073
- Last updated2004-07-05 v1
- ChecksumD31E9876D146519A
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AE016958 EMBL· GenBank· DDBJ | AAS04853.1 EMBL· GenBank· DDBJ | Genomic DNA |