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MetaCyc Protein: pyruvate dehydrogenase

Gene: aceE Accession Numbers: EG10024 (MetaCyc), b0114, ECK0113

Component of: pyruvatedeh-cplx (extended summary available)

Subunit composition of pyruvate dehydrogenase = [AceE]2
         subunit of E1p component of pyruvate dehydrogenase complex = AceE

Summary:
It is sometimes confusing that this component and the multi-enzyme complex both carry the same name.

Citations: [Stephens83, Graham89]

Locations: membrane, cytosol

Map Position: [123,017 -> 125,680]

Molecular Weight of Polypeptide: 99.668 kD (from nucleotide sequence)

pI: 5.76

Unification Links: ASAP:ABE-0000397 , CGSC:1050 , DIP:DIP-9039N , DisProt:DP00427 , EchoBASE:EB0023 , EcoGene:EG10024 , EcoliWiki:b0114 , Mint:MINT-1261483 , OU-Microarray:b0114 , PortEco:aceE , PR:PRO_000022038 , Pride:P0AFG8 , Protein Model Portal:P0AFG8 , RefSeq:NP_414656 , RegulonDB:EG10024 , SMR:P0AFG8 , String:511145.b0114 , Swiss-Model:P0AFG8 , UniProt:P0AFG8

Relationship Links: InterPro:IN-FAMILY:IPR004660 , InterPro:IN-FAMILY:IPR005474 , InterPro:IN-FAMILY:IPR009014 , InterPro:IN-FAMILY:IPR029061 , PDB:Structure:1L8A , PDB:Structure:1RP7 , PDB:Structure:2G25 , PDB:Structure:2G28 , PDB:Structure:2G67 , PDB:Structure:2IEA , PDB:Structure:2QTA , PDB:Structure:2QTC , Pfam:IN-FAMILY:PF00456

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Instance reaction of [a [lipoyl-carrier protein] N6-dihydrolipoyl-L-lysine + NAD+ → a [lipoyl-carrier protein] N6-lipoyl-L-lysine + NADH + H+] (1.8.1.4):
i2: a [glycine-cleavage complex H protein] N6-dihydrolipoyl-L-lysine + NAD+ ↔ a [glycine-cleavage complex H protein] N6-lipoyl-L-lysine + NADH + H+ (1.8.1.4)

GO Terms:

Biological Process: GO:0006096 - glycolytic process Inferred by computational analysis [UniProtGOA11a]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA01a]
Molecular Function: GO:0004738 - pyruvate dehydrogenase activity Inferred from experiment [Langley77]
GO:0005515 - protein binding Inferred from experiment [Arifuzzaman06, Butland05]
GO:0042802 - identical protein binding Inferred from experiment [Lasserre06]
GO:0003824 - catalytic activity Inferred by computational analysis [GOA01a]
GO:0004739 - pyruvate dehydrogenase (acetyl-transferring) activity Inferred by computational analysis [GOA01]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Lasserre06]
GO:0016020 - membrane Inferred from experiment [Lasserre06]

MultiFun Terms: metabolism carbon utilization carbon compounds
metabolism central intermediary metabolism glyoxylate degradation
metabolism energy metabolism, carbon pyruvate dehydrogenase

Credits:
Imported from EcoCyc 27-Jan-2015 by Paley S , SRI International


Subunit of: pyruvatedeh-cplx

Subunit composition of pyruvatedeh-cplx = [(Lpd)2]6[(AceE)2]12[AceF]24
         lipoamide dehydrogenase = (Lpd)2 (extended summary available)
                 E3 monomer = Lpd
         pyruvate dehydrogenase = (AceE)2 (summary available)
                 subunit of E1p component of pyruvate dehydrogenase complex = AceE

Summary:
Pyruvate dehydrogenase is one of the most complicated enzyme systems known. The self-assembling complex is composed of multiple copies of three enzymes: E1, E2 and E3, in stoichiometry of 24:24:12, respectively (12 AceE dimers, a 24-subunit AceF core, and 6 LpdA dimers) [Reed75, Bates77, Yang85, CaJacob85, Angelides79].

AceF, the "E2" or "core" component of the pyruvate dehydrogenase multienzyme complex, assembles into a 24-subunit [Angelides79] cube [Yang85, Wagenknecht90]. The E1 dimers of the pyruvate dehydrogenase multienzyme complex catalyze acetylation of the lipoate moieties that are attached to the E2 subunits [Danson78]. The E2 subunits (AceF) also exhibit transacetylation [Stanley81]. The structure of the pyruvate dehydrogenase multienzyme complex and the spatial distribution of the E2 lipoyl moieties have been studied by scanning transmission electron microscopy [Yang94]. Electron cryotomography showed that the E1 and E3 subunits are flexibly tethered to the E2 core [Murphy05].

The E3 component is shared with 2-oxoglutarate dehydrogenase and glycine cleavage multi-enzyme complexes. E1 and E2 differ slightly between 2-oxoglutarate and pyruvate complexes, and are designated (o) and (p) to distinguish them. Substrate is channeled through the catalytic reactions by attachment in thioester linkage to lipoyl groups via so-called 'swinging arm', carrying substrate molecules to successive active sites [Perham87].

The reaction catalyzed by the pyruvate dehydrogenase multienzyme complex is the gateway to the TCA cycle, producing acetylCoA for the first reaction. In animals, the reaction is regulated by phosphorylation of the E1 component, but not in E. coli [Patel90].

Credits:
Imported from EcoCyc 27-Jan-2015 by Paley S , SRI International


Sequence Features

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Link97, UniProt11]
UniProt: Removed.
Chain 2 -> 887
[UniProt09]
UniProt: Pyruvate dehydrogenase E1 component;
Sequence-Conflict 146
[Stephens83, UniProt13]
UniProt: (in Ref. 1; CAA24740).
Metal-Binding-Site 231
[UniProt10]
UniProt: Magnesium;
Metal-Binding-Site 261
[UniProt10]
UniProt: Magnesium;
Metal-Binding-Site 263
[UniProt10]
UniProt: Magnesium; via carbonyl oxygen;
Sequence-Conflict 276
[Stephens83, UniProt13]
UniProt: (in Ref. 1; CAA24740).
Acetylation-Modification 716
[Zhang09a, UniProt11]
UniProt: N6-acetyllysine.

History:
10/20/97 Gene b0114 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10024; confirmed by SwissProt match.


References

Angelides79: Angelides KJ, Akiyama SK, Hammes GG (1979). "Subunit stoichiometry and molecular weight of the pyruvate dehydrogenase multienzyme complex from Escherichia coli." Proc Natl Acad Sci U S A 1979;76(7);3279-83. PMID: 386335

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

Bates77: Bates DL, Danson MJ, Hale G, Hooper EA, Perham RN (1977). "Self-assembly and catalytic activity of the pyruvate dehydrogenase multienzyme complex of Escherichia coli." Nature 268(5618);313-6. PMID: 329143

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

CaJacob85: CaJacob CA, Frey PA, Hainfeld JF, Wall JS, Yang H (1985). "Escherichia coli pyruvate dehydrogenase complex: particle masses of the complex and component enzymes measured by scanning transmission electron microscopy." Biochemistry 1985;24(10);2425-31. PMID: 3925985

Danson78: Danson MJ, Hooper EA, Perham RN (1978). "Intramolecular coupling of active sites in the pyruvate dehydrogenase multienzyme complex of Escherichia coli." Biochem J 175(1);193-8. PMID: 367364

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Graham89: Graham LD, Packman LC, Perham RN (1989). "Kinetics and specificity of reductive acylation of lipoyl domains from 2-oxo acid dehydrogenase multienzyme complexes." Biochemistry 1989;28(4);1574-81. PMID: 2655695

Langley77: Langley D, Guest JR (1977). "Biochemical genetics of the alpha-keto acid dehydrogenase complexes of Escherichia coli K12: isolation and biochemical properties of deletion mutants." J Gen Microbiol 99(2);263-76. PMID: 327021

Lasserre06: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726

Link97: Link AJ, Robison K, Church GM (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18(8);1259-313. PMID: 9298646

Murphy05: Murphy GE, Jensen GJ (2005). "Electron cryotomography of the E. coli pyruvate and 2-oxoglutarate dehydrogenase complexes." Structure 13(12);1765-73. PMID: 16338405

Patel90: Patel MS, Roche TE (1990). "Molecular biology and biochemistry of pyruvate dehydrogenase complexes." FASEB J 1990;4(14);3224-33. PMID: 2227213

Perham87: Perham RN, Packman LC, Radford SE (1987). "2-Oxo acid dehydrogenase multi-enzyme complexes: in the beginning and halfway there." Biochem Soc Symp 1987;54;67-81. PMID: 3332999

Reed75: Reed LJ, Pettit FH, Eley MH, Hamilton L, Collins JH, Oliver RM (1975). "Reconstitution of the Escherichia coli pyruvate dehydrogenase complex." Proc Natl Acad Sci U S A 1975;72(8);3068-72. PMID: 1103138

Stanley81: Stanley CJ, Packman LC, Danson MJ, Henderson CE, Perham RN (1981). "Intramolecular coupling of active sites in the pyruvate dehydrogenase multienzyme complexes from bacterial and mammalian sources." Biochem J 195(3);715-21. PMID: 7032507

Stephens83: Stephens PE, Darlison MG, Lewis HM, Guest JR (1983). "The pyruvate dehydrogenase complex of Escherichia coli K12. Nucleotide sequence encoding the pyruvate dehydrogenase component." Eur J Biochem 1983;133(1);155-62. PMID: 6343085

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt13: UniProt Consortium (2013). "UniProt version 2013-08 released on 2013-08-01 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Wagenknecht90: Wagenknecht T, Grassucci R, Schaak D (1990). "Cryoelectron microscopy of frozen-hydrated alpha-ketoacid dehydrogenase complexes from Escherichia coli." J Biol Chem 265(36);22402-8. PMID: 2266132

Yang85: Yang HC, Hainfeld JF, Wall JS, Frey PA (1985). "Quaternary structure of pyruvate dehydrogenase complex from Escherichia coli." J Biol Chem 1985;260(30);16049-51. PMID: 3905803

Yang94: Yang YS, Datta A, Hainfeld JF, Furuya FR, Wall JS, Frey PA (1994). "Mapping the lipoyl groups of the pyruvate dehydrogenase complex by use of gold cluster labels and scanning transmission electron microscopy." Biochemistry 33(32);9428-37. PMID: 7520749

Zhang09a: Zhang J, Sprung R, Pei J, Tan X, Kim S, Zhu H, Liu CF, Grishin NV, Zhao Y (2009). "Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli." Mol Cell Proteomics 8(2);215-25. PMID: 18723842


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Sat Mar 28, 2015, biocyc12.