UniProtKB - P07003 (POXB_ECOLI)
Protein
Pyruvate dehydrogenase [ubiquinone]
Gene
poxB
Organism
Escherichia coli (strain K12)
Status
Functioni
A peripheral cell membrane enzyme that catalyzes the oxidative decarboxylation of pyruvate to form acetate and CO2. It channels electrons from the cytoplasm to the respiratory chain at the cell membrane via ubiquinone (By similarity) (PubMed:18988747, PubMed:2663858, PubMed:365232). The main pathway for acetate production during stationary phase (PubMed:16080684).UniRule annotation4 Publications
Catalytic activityi
- a ubiquinone + H2O + pyruvate = a ubiquinol + acetate + CO2UniRule annotation1 Publication6 PublicationsEC:1.2.5.1UniRule annotation1 Publication6 Publications
Cofactori
Protein has several cofactor binding sites:- FADUniRule annotation2 PublicationsNote: Binds 1 FAD per subunit.UniRule annotation1 Publication
- Mg2+UniRule annotation3 PublicationsNote: Binds 1 Mg2+ ion per subunit; Mn2+ is also functional. The Me2+-thiamine diphosphate complex is the true cofactor.UniRule annotation2 Publications
- thiamine diphosphateUniRule annotation3 PublicationsNote: Binds 1 thiamine pyrophosphate per subunit.UniRule annotation2 Publications
Activity regulationi
The C-terminus inhibits activity; it has to move for the enzyme to be active (PubMed:18988747). Activated by lipid-binding, which occurs via the C-terminus; detergents also activate the enzyme (PubMed:334770, PubMed:334771, PubMed:2663858, PubMed:18988747). Specifically activated by palmitic acid; 12 (lauric) and 14-carbon (myristic) fatty acids as well as unsaturated 16 and 18-carbon fatty acids also activate the enzyme (PubMed:6385860). Lipid affinity is increased in the presence of pyruvate plus the thiamine pyrophosphate cofactor (PubMed:334770, PubMed:334771, PubMed:2663858, PubMed:18988747).UniRule annotation5 Publications
Kineticsi
kcat is 7 sec(-1) for non-activated, 200 sec(-1) for activated form.1 Publication
- KM=90 mM for pyruvate, non-activated form1 Publication
- KM=12 mM for pyruvate, activated form1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 50 | Thiamine pyrophosphateUniRule annotationCombined sources1 Publication | 1 | |
Binding sitei | 210 | FADCombined sources1 Publication | 1 | |
Binding sitei | 292 | FADUniRule annotationCombined sources1 Publication | 1 | |
Binding sitei | 297 | FADCombined sources1 Publication | 1 | |
Binding sitei | 382 | Thiamine pyrophosphateCombined sources1 Publication | 1 | |
Metal bindingi | 433 | MagnesiumUniRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 460 | MagnesiumUniRule annotationCombined sources1 Publication | 1 | |
Metal bindingi | 462 | Magnesium; via carbonyl oxygenCombined sources1 Publication | 1 | |
Sitei | 465 | Moves into active site upon enzyme activation, plays a role in electron transferUniRule annotation1 Publication | 1 | |
Sitei | 549 – 550 | In vitro cleavage to yield alpha-peptide1 Publication | 2 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 234 – 235 | FADCombined sources1 Publication | 2 | |
Nucleotide bindingi | 251 – 254 | FADUniRule annotationCombined sources1 Publication | 4 | |
Nucleotide bindingi | 274 – 278 | FADUniRule annotationCombined sources1 Publication | 5 | |
Nucleotide bindingi | 311 – 312 | FADCombined sources1 Publication | 2 | |
Nucleotide bindingi | 403 – 404 | FADCombined sources1 Publication | 2 |
GO - Molecular functioni
- flavin adenine dinucleotide binding Source: EcoCyc
- identical protein binding Source: EcoCyc
- lipid binding Source: EcoCyc
- magnesium ion binding Source: EcoCyc
- pyruvate dehydrogenase (quinone) activity Source: EcoCyc
- thiamine pyrophosphate binding Source: EcoCyc
GO - Biological processi
- pyruvate catabolic process Source: EcoCyc
- pyruvate metabolic process Source: EcoCyc
Keywordsi
Molecular function | Oxidoreductase |
Ligand | FAD, Flavoprotein, Lipid-binding, Magnesium, Metal-binding, Nucleotide-binding, Pyruvate, Thiamine pyrophosphate, Ubiquinone |
Enzyme and pathway databases
BioCyci | EcoCyc:PYRUVOXID-MONOMER MetaCyc:PYRUVOXID-MONOMER |
BRENDAi | 1.2.5.1, 2026 |
Names & Taxonomyi
Protein namesi | Recommended name: Pyruvate dehydrogenase [ubiquinone]UniRule annotation (EC:1.2.5.1UniRule annotation2 Publications)Alternative name(s): Pyruvate oxidaseUniRule annotation Short name: POXUniRule annotation Pyruvate:ubiquinone-8 oxidoreductaseUniRule annotation |
Gene namesi | Name:poxBUniRule annotation Ordered Locus Names:b0871, JW0855 |
Organismi | Escherichia coli (strain K12) |
Taxonomic identifieri | 83333 [NCBI] |
Taxonomic lineagei | Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › |
Proteomesi |
|
Subcellular locationi
- Cell inner membrane UniRule annotation1 Publication1 Publication; Peripheral membrane protein UniRule annotation1 Publication1 Publication; Cytoplasmic side UniRule annotation1 Publication
GO - Cellular componenti
- cytosol Source: EcoCyc
- plasma membrane Source: UniProtKB-SubCell
- protein-containing complex Source: EcoCyc
Keywords - Cellular componenti
Cell inner membrane, Cell membrane, MembranePathology & Biotechi
Disruption phenotypei
Not essential it can be deleted.1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 533 | A → T in poxB11; poor activity in vivo, no longer activated by lipids. 1 Publication | 1 | |
Mutagenesisi | 549 – 572 | Missing in poxB6. Inactive in vivo, does not complement inactive mutants. Active in vitro, no longer activated by nor binds to, detergents. 2 PublicationsAdd BLAST | 24 | |
Mutagenesisi | 553 | A → V in poxB14; poor activity in vivo, no longer activated by lipids. 1 Publication | 1 | |
Mutagenesisi | 560 | D → P in poxB15; normal activity. 1 Publication | 1 | |
Mutagenesisi | 564 – 572 | Missing in poxB7 Inactive in vivo, reduced activity in vitro. 1 Publication | 9 | |
Mutagenesisi | 564 | E → P in poxB16; loss of activity, weakly activated by cleavage. 1 Publication | 1 | |
Mutagenesisi | 570 – 572 | Missing in poxB8; reduced activity in vitro, not activated by lipids. 1 Publication | 3 | |
Mutagenesisi | 572 | R → G in poxB10; reduced activity in vivo and in vitro; may interact less with membranes. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL3380 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000044606 | 1 – 572 | Pyruvate dehydrogenase [ubiquinone]Add BLAST | 572 |
Post-translational modificationi
Activated by limited proteolytic digestion in vitro. This cleavage produces a peptide (alpha-peptide) and mimics the activation of enzyme by phospholipids (PubMed:5336022, PubMed:3902830, PubMed:334770, PubMed:334771). Protease activation and lipid-activation are mutually exclusive. Proteolytic cleavage results in the loss of the high affinity lipid-binding site of the enzyme; the cleaved protein is no longer activated by lipids or detergents (PubMed:334771, PubMed:2663858). The proteolytically cleaved enzyme does not represent a functional cleavage in vivo (PubMed:3527254).6 Publications
Proteomic databases
jPOSTi | P07003 |
PaxDbi | P07003 |
PRIDEi | P07003 |
2D gel databases
SWISS-2DPAGEi | P07003 |
Expressioni
Inductioni
Interactioni
Subunit structurei
Homotetramer.
UniRule annotation1 Publication2 PublicationsBinary interactionsi
P07003
With | #Exp. | IntAct |
---|---|---|
itself | 3 | EBI-909338,EBI-909338 |
GO - Molecular functioni
- identical protein binding Source: EcoCyc
Protein-protein interaction databases
BioGRIDi | 4262101, 20 interactors 850492, 1 interactor |
DIPi | DIP-36216N |
IntActi | P07003, 4 interactors |
STRINGi | 511145.b0871 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P07003 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P07003 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 182 | Pyr domainUniRule annotation1 PublicationAdd BLAST | 182 | |
Regioni | 183 – 334 | FAD-binding domainUniRule annotation1 PublicationAdd BLAST | 152 | |
Regioni | 335 – 530 | PP-binding domainUniRule annotation1 PublicationAdd BLAST | 196 | |
Regioni | 406 – 408 | Thiamine pyrophosphate bindingUniRule annotationCombined sources1 Publication | 3 | |
Regioni | 433 – 435 | Thiamine pyrophosphate bindingUniRule annotationCombined sources1 Publication | 3 | |
Regioni | 460 – 466 | Thiamine pyrophosphate bindingUniRule annotationCombined sources1 Publication | 7 | |
Regioni | 531 – 572 | Membrane-binding domainUniRule annotation1 PublicationAdd BLAST | 42 |
Domaini
Has 4 domains; the Pyr domain which binds the pyrimidine moiety of the thiamine pyrophosphate cofactor, the FAD-binding domain, the PP-binding domain which binds the pyrophosphate portion of thiamine pyrophosphate and the C-terminal membrane binding region, which includes the in vitro-derived alpha-peptide (residues 550-572). The C-terminus is held closely against the rest of the protein and covers the active site; during activation it detaches from the rest of the protein and folds into an amphipathic helix upon membrane binding. Comparison of full-length and proteolyzed structures shows activation is a result of conformational changes that expose the active site.1 Publication
Sequence similaritiesi
Belongs to the TPP enzyme family.UniRule annotation
Phylogenomic databases
eggNOGi | COG0028, Bacteria |
HOGENOMi | CLU_013748_3_0_6 |
InParanoidi | P07003 |
PhylomeDBi | P07003 |
Family and domain databases
HAMAPi | MF_00850, POX, 1 hit |
InterProi | View protein in InterPro IPR029035, DHS-like_NAD/FAD-binding_dom IPR029061, THDP-binding IPR012000, Thiamin_PyroP_enz_cen_dom IPR012001, Thiamin_PyroP_enz_TPP-bd_dom IPR000399, TPP-bd_CS IPR011766, TPP_enzyme-bd_C |
Pfami | View protein in Pfam PF02775, TPP_enzyme_C, 1 hit PF00205, TPP_enzyme_M, 1 hit PF02776, TPP_enzyme_N, 1 hit |
SUPFAMi | SSF52467, SSF52467, 1 hit SSF52518, SSF52518, 2 hits |
PROSITEi | View protein in PROSITE PS00187, TPP_ENZYMES, 1 hit |
i Sequence
Sequence statusi: Complete.
P07003-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKQTVAAYIA KTLESAGVKR IWGVTGDSLN GLSDSLNRMG TIEWMSTRHE
60 70 80 90 100
EVAAFAAGAE AQLSGELAVC AGSCGPGNLH LINGLFDCHR NHVPVLAIAA
110 120 130 140 150
HIPSSEIGSG YFQETHPQEL FRECSHYCEL VSSPEQIPQV LAIAMRKAVL
160 170 180 190 200
NRGVSVVVLP GDVALKPAPE GATMHWYHAP QPVVTPEEEE LRKLAQLLRY
210 220 230 240 250
SSNIALMCGS GCAGAHKELV EFAGKIKAPI VHALRGKEHV EYDNPYDVGM
260 270 280 290 300
TGLIGFSSGF HTMMNADTLV LLGTQFPYRA FYPTDAKIIQ IDINPASIGA
310 320 330 340 350
HSKVDMALVG DIKSTLRALL PLVEEKADRK FLDKALEDYR DARKGLDDLA
360 370 380 390 400
KPSEKAIHPQ YLAQQISHFA ADDAIFTCDV GTPTVWAARY LKMNGKRRLL
410 420 430 440 450
GSFNHGSMAN AMPQALGAQA TEPERQVVAM CGDGGFSMLM GDFLSVVQMK
460 470 480 490 500
LPVKIVVFNN SVLGFVAMEM KAGGYLTDGT ELHDTNFARI AEACGITGIR
510 520 530 540 550
VEKASEVDEA LQRAFSIDGP VLVDVVVAKE ELAIPPQIKL EQAKGFSLYM
560 570
LRAIISGRGD EVIELAKTNW LR
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 364 – 365 | QQ → HE in AAB59101 (PubMed:2663858).Curated | 2 | |
Sequence conflicti | 364 – 365 | QQ → HE in AAB59102 (PubMed:2663858).Curated | 2 | |
Sequence conflicti | 414 – 416 | QAL → HGV in AAB59101 (PubMed:2663858).Curated | 3 | |
Sequence conflicti | 414 – 416 | QAL → HGV in AAB59102 (PubMed:2663858).Curated | 3 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X04105 Genomic DNA Translation: CAA27725.1 U00096 Genomic DNA Translation: AAC73958.1 AP009048 Genomic DNA Translation: BAA35585.1 S73268 Genomic DNA Translation: AAB31180.1 M28208 Genomic DNA Translation: AAB59101.1 L47688 Genomic DNA Translation: AAB59102.1 L47689 Genomic DNA Translation: AAB59103.1 L47690 Genomic DNA Translation: AAB59104.1 L47691 Genomic DNA Translation: AAB59105.1 L47692 Genomic DNA Translation: AAB59106.1 L47693 Genomic DNA Translation: AAB59107.1 L47694 Genomic DNA Translation: AAB59108.1 L47695 Genomic DNA Translation: AAB59109.1 |
PIRi | A23648, DEECPC |
RefSeqi | NP_415392.1, NC_000913.3 WP_000815337.1, NZ_SSZK01000002.1 |
Genome annotation databases
EnsemblBacteriai | AAC73958; AAC73958; b0871 BAA35585; BAA35585; BAA35585 |
GeneIDi | 946132 |
KEGGi | ecj:JW0855 eco:b0871 |
PATRICi | fig|1411691.4.peg.1406 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X04105 Genomic DNA Translation: CAA27725.1 U00096 Genomic DNA Translation: AAC73958.1 AP009048 Genomic DNA Translation: BAA35585.1 S73268 Genomic DNA Translation: AAB31180.1 M28208 Genomic DNA Translation: AAB59101.1 L47688 Genomic DNA Translation: AAB59102.1 L47689 Genomic DNA Translation: AAB59103.1 L47690 Genomic DNA Translation: AAB59104.1 L47691 Genomic DNA Translation: AAB59105.1 L47692 Genomic DNA Translation: AAB59106.1 L47693 Genomic DNA Translation: AAB59107.1 L47694 Genomic DNA Translation: AAB59108.1 L47695 Genomic DNA Translation: AAB59109.1 |
PIRi | A23648, DEECPC |
RefSeqi | NP_415392.1, NC_000913.3 WP_000815337.1, NZ_SSZK01000002.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3EY9 | X-ray | 2.90 | A/B | 1-572 | [»] | |
3EYA | X-ray | 2.50 | A/B/C/D/E/F/G/H/I/J/K/L | 1-549 | [»] | |
SMRi | P07003 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 4262101, 20 interactors 850492, 1 interactor |
DIPi | DIP-36216N |
IntActi | P07003, 4 interactors |
STRINGi | 511145.b0871 |
Chemistry databases
ChEMBLi | CHEMBL3380 |
2D gel databases
SWISS-2DPAGEi | P07003 |
Proteomic databases
jPOSTi | P07003 |
PaxDbi | P07003 |
PRIDEi | P07003 |
Genome annotation databases
EnsemblBacteriai | AAC73958; AAC73958; b0871 BAA35585; BAA35585; BAA35585 |
GeneIDi | 946132 |
KEGGi | ecj:JW0855 eco:b0871 |
PATRICi | fig|1411691.4.peg.1406 |
Organism-specific databases
EchoBASEi | EB0747 |
Phylogenomic databases
eggNOGi | COG0028, Bacteria |
HOGENOMi | CLU_013748_3_0_6 |
InParanoidi | P07003 |
PhylomeDBi | P07003 |
Enzyme and pathway databases
BioCyci | EcoCyc:PYRUVOXID-MONOMER MetaCyc:PYRUVOXID-MONOMER |
BRENDAi | 1.2.5.1, 2026 |
Miscellaneous databases
EvolutionaryTracei | P07003 |
PROi | PR:P07003 |
Family and domain databases
HAMAPi | MF_00850, POX, 1 hit |
InterProi | View protein in InterPro IPR029035, DHS-like_NAD/FAD-binding_dom IPR029061, THDP-binding IPR012000, Thiamin_PyroP_enz_cen_dom IPR012001, Thiamin_PyroP_enz_TPP-bd_dom IPR000399, TPP-bd_CS IPR011766, TPP_enzyme-bd_C |
Pfami | View protein in Pfam PF02775, TPP_enzyme_C, 1 hit PF00205, TPP_enzyme_M, 1 hit PF02776, TPP_enzyme_N, 1 hit |
SUPFAMi | SSF52467, SSF52467, 1 hit SSF52518, SSF52518, 2 hits |
PROSITEi | View protein in PROSITE PS00187, TPP_ENZYMES, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | POXB_ECOLI | |
Accessioni | P07003Primary (citable) accession number: P07003 Secondary accession number(s): Q47513 Q47520 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1988 |
Last sequence update: | April 1, 1988 | |
Last modified: | December 2, 2020 | |
This is version 173 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Prokaryotic Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families