P9WIS4 · KGD_MYCTO
- ProteinMultifunctional 2-oxoglutarate metabolism enzyme
- Genekgd
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids1231 (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, which can endow M.tuberculosis with the metabolic plasticity required for growth on diverse host-derived carbon sources. Appears to play a predominant role in growth on carbohydrates as the sole carbon source, and only a minimal role during growth on fatty acids (By similarity).
Catalytic activity
- 2-oxoglutarate + glyoxylate + H+ = 2-hydroxy-3-oxoadipate + CO2
Cofactor
Protein has several cofactor binding sites:
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 | 316 | Proton acceptor; for succinyltransferase activity | ||||
Sequence: H | ||||||
Binding site | 542 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 581 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 606 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 606 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 608 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 649 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 649 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 650 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 651 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 682 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 682 | thiamine diphosphate (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 684 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 1024 | 2-oxoglutarate (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 1042 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: T | ||||||
Binding site | 1058 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: R | ||||||
Binding site | 1093 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: K | ||||||
Binding site | 1096 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: S | ||||||
Binding site | 1146 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: Q | ||||||
Binding site | 1153 | acetyl-CoA (UniProtKB | ChEBI); allosteric activator | ||||
Sequence: R | ||||||
Binding site | 1154 | 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 tuberculosis complex
Accessions
- Primary accessionP9WIS4
- Secondary accessions
Proteomes
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000427954 | 1-1231 | Multifunctional 2-oxoglutarate metabolism enzyme | |||
Sequence: MANISSPFGQNEWLVEEMYRKFRDDPSSVDPSWHEFLVDYSPEPTSQPAAEPTRVTSPLVAERAAAAAPQAPPKPADTAAAGNGVVAALAAKTAVPPPAEGDEVAVLRGAAAAVVKNMSASLEVPTATSVRAVPAKLLIDNRIVINNQLKRTRGGKISFTHLLGYALVQAVKKFPNMNRHYTEVDGKPTAVTPAHTNLGLAIDLQGKDGKRSLVVAGIKRCETMRFAQFVTAYEDIVRRARDGKLTTEDFAGVTISLTNPGTIGTVHSVPRLMPGQGAIIGVGAMEYPAEFQGASEERIAELGIGKLITLTSTYDHRIIQGAESGDFLRTIHELLLSDGFWDEVFRELSIPYLPVRWSTDNPDSIVDKNARVMNLIAAYRNRGHLMADTDPLRLDKARFRSHPDLEVLTHGLTLWDLDRVFKVDGFAGAQYKKLRDVLGLLRDAYCRHIGVEYAHILDPEQKEWLEQRVETKHVKPTVAQQKYILSKLNAAEAFETFLQTKYVGQKRFSLEGAESVIPMMDAAIDQCAEHGLDEVVIGMPHRGRLNVLANIVGKPYSQIFTEFEGNLNPSQAHGSGDVKYHLGATGLYLQMFGDNDIQVSLTANPSHLEAVDPVLEGLVRAKQDLLDHGSIDSDGQRAFSVVPLMLHGDAAFAGQGVVAETLNLANLPGYRVGGTIHIIVNNQIGFTTAPEYSRSSEYCTDVAKMIGAPIFHVNGDDPEACVWVARLAVDFRQRFKKDVVIDMLCYRRRGHNEGDDPSMTNPYVYDVVDTKRGARKSYTEALIGRGDISMKEAEDALRDYQGQLERVFNEVRELEKHGVQPSESVESDQMIPAGLATAVDKSLLARIGDAFLALPNGFTAHPRVQPVLEKRREMAYEGKIDWAFGELLALGSLVAEGKLVRLSGQDSRRGTFSQRHSVLIDRHTGEEFTPLQLLATNSDGSPTGGKFLVYDSPLSEYAAVGFEYGYTVGNPDAVVLWEAQFGDFVNGAQSIIDEFISSGEAKWGQLSNVVLLLPHGHEGQGPDHTSARIERFLQLWAEGSMTIAMPSTPSNYFHLLRRHALDGIQRPLIVFTPKSMLRHKAAVSEIKDFTEIKFRSVLEEPTYEDGIGDRNKVSRILLTSGKLYYELAARKAKDNRNDLAIVRLEQLAPLPRRRLRETLDRYENVKEFFWVQEEPANQGAWPRFGLELPELLPDKLAGIKRISRRAMSAPSSGSSKVHAVEQQEILDEAFG |
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).
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: MANISSPFGQNEWLVEEMYRKFRDDPSSVDPSWHEFLVDYS | ||||||
Region | 38-79 | Disordered | ||||
Sequence: VDYSPEPTSQPAAEPTRVTSPLVAERAAAAAPQAPPKPADTA | ||||||
Region | 42-88 | Linker | ||||
Sequence: PEPTSQPAAEPTRVTSPLVAERAAAAAPQAPPKPADTAAAGNGVVAA | ||||||
Region | 89-337 | Succinyltransferase E2 | ||||
Sequence: LAAKTAVPPPAEGDEVAVLRGAAAAVVKNMSASLEVPTATSVRAVPAKLLIDNRIVINNQLKRTRGGKISFTHLLGYALVQAVKKFPNMNRHYTEVDGKPTAVTPAHTNLGLAIDLQGKDGKRSLVVAGIKRCETMRFAQFVTAYEDIVRRARDGKLTTEDFAGVTISLTNPGTIGTVHSVPRLMPGQGAIIGVGAMEYPAEFQGASEERIAELGIGKLITLTSTYDHRIIQGAESGDFLRTIHELLLS | ||||||
Region | 338-1231 | 2-oxoglutarate dehydrogenase E1, C-terminal part | ||||
Sequence: DGFWDEVFRELSIPYLPVRWSTDNPDSIVDKNARVMNLIAAYRNRGHLMADTDPLRLDKARFRSHPDLEVLTHGLTLWDLDRVFKVDGFAGAQYKKLRDVLGLLRDAYCRHIGVEYAHILDPEQKEWLEQRVETKHVKPTVAQQKYILSKLNAAEAFETFLQTKYVGQKRFSLEGAESVIPMMDAAIDQCAEHGLDEVVIGMPHRGRLNVLANIVGKPYSQIFTEFEGNLNPSQAHGSGDVKYHLGATGLYLQMFGDNDIQVSLTANPSHLEAVDPVLEGLVRAKQDLLDHGSIDSDGQRAFSVVPLMLHGDAAFAGQGVVAETLNLANLPGYRVGGTIHIIVNNQIGFTTAPEYSRSSEYCTDVAKMIGAPIFHVNGDDPEACVWVARLAVDFRQRFKKDVVIDMLCYRRRGHNEGDDPSMTNPYVYDVVDTKRGARKSYTEALIGRGDISMKEAEDALRDYQGQLERVFNEVRELEKHGVQPSESVESDQMIPAGLATAVDKSLLARIGDAFLALPNGFTAHPRVQPVLEKRREMAYEGKIDWAFGELLALGSLVAEGKLVRLSGQDSRRGTFSQRHSVLIDRHTGEEFTPLQLLATNSDGSPTGGKFLVYDSPLSEYAAVGFEYGYTVGNPDAVVLWEAQFGDFVNGAQSIIDEFISSGEAKWGQLSNVVLLLPHGHEGQGPDHTSARIERFLQLWAEGSMTIAMPSTPSNYFHLLRRHALDGIQRPLIVFTPKSMLRHKAAVSEIKDFTEIKFRSVLEEPTYEDGIGDRNKVSRILLTSGKLYYELAARKAKDNRNDLAIVRLEQLAPLPRRRLRETLDRYENVKEFFWVQEEPANQGAWPRFGLELPELLPDKLAGIKRISRRAMSAPSSGSSKVHAVEQQEILDEAFG | ||||||
Coiled coil | 787-817 | |||||
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
- Length1,231
- Mass (Da)135,902
- Last updated2014-04-16 v1
- Checksum96C255612BA12889
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AE000516 EMBL· GenBank· DDBJ | AAK45544.1 EMBL· GenBank· DDBJ | Genomic DNA |