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Overview for MACiE Entry M0275

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General Information

EC Number: 1.2.2.2 (A member of the Oxidoreductases, Acting on the aldehyde or oxo group of donors, With a cytochrome as acceptor)

Enzyme Name: pyruvate dehydrogenase (cytochrome)

Biological Species: Escherichia coli (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

Representative PDB Code: 3ey9 - STRUCTURAL BASIS FOR MEMBRANE BINDING AND CATALYTICACTIVATION OF THE PERIPHERAL MEMBRANE ENZYME PYRUVATEOXIDASE FROM ESCHERICHIA COLI (Resolution = 2.90 Å).

Catalytic CATH Codes:

  • Unassigned Domain

Display structure information

Overall Reaction:

Image of ubiquinone

Image of water

Image of pyruvate

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Image of carbon dioxide

Image of ubiquinol

Image of acetate

ubiquinone
C00399
CHEBI:16389
water
C00001
CHEBI:15377
pyruvate
C00022
CHEBI:15361
carbon dioxide
C00011
CHEBI:16526
ubiquinol
C00390
CHEBI:17976
acetate
C00033
CHEBI:30089

Overall Comment: Pyruvate oxidase supports aerobic growth in E. coli as a backup system to the pyruvate dehydrogenase multienzyme complex.


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Stepwise Description of the Reaction

Step 1Glu50' deprotonates the thiamine diphosphate cofactor at the N1 position. This initiates double bond rearrangement which results in the deprotonation of the N=CH-S group. This activates the cofactor towards electrophilic attack.
Step 2The carbanion of thiamine diphosphate initiates a nucleophilic attack on the carbonyl carbon of pyruvate in an addition reaction. The conjugated double bond system of the cofactor undergoes rearrangement which results in the deprotonation of Glu50'.
Step 3The covalently bound pyruvate undergoes decarboxylation.
Step 4A single electron is transferred from the high energy thamine diphosphate enamine intermediate to the FAD cofactor. This results in bond order rearrangement and deprotonation of the alcohol group present on the intermediate.
Step 5Tautomerisation of the radical intermediate occurs.
Step 6The thiamine ring nitrogen acts as an electron sink in the formation of a second radical tautomer.
Step 7Water acts as a nucleophile towards the neutral radical thiamine diphosphate-pyruvate adduct.
Step 8The hydrolysis product delivers a second reducing equivalent to the FAD cofactor.
Step 9The tetrahedral intermediate collapses, eliminating acetate and regenerating the carbanionic form of thiamine diphosphate.
Step 10The thiamine diphosphate cofactor is regenerated on deprotonation of the pyruvate product.
Step 11Ubiquinone receives one reducing equivalent from the reduced FAD cofactor.
Step 12The second reducing equivalent is transferred to the bound ubiquinone. This forms the electron transport agent ubiquinol and regenerates the FAD cofactor.

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Catalytic Residues Involved

Type Number Chain Location of Function
Glu 50 B Side Chain
Gln 133 A Side Chain
Val 380 A Side Chain
Phe 122 A Side Chain
Phe 465 A Side Chain

Organic Cofactors for M0275

Type Identity Chain
FAD FAD 612 A Overview
Thiamine diphosphate TDP 611 A Overview

Metal Cofactors for M0275

Type Het group Number Chain
magnesium MG 616 A Overview

References

  1. P. Neumann et al. (2008), Proc. Natl Acad. Sci. USA, 105, 17390-17395. Structural basis for membrane binding and catalytic activation of the peripheral membrane enzyme pyruvate oxidase from Escherichia coli.
    Medline: 18988747
  2. K. Tittmann et al. (2009), FEBS Journal, 276, 2454-2468. Reaction mechanisms of thiamin diphosphate enzymes: redox reactions.
    Medline: 19476487
  3. Y.Y Chang et al. (2000), Biochem. J., 352, 717-124. Conversion of Escherichia coli pyruvate oxidase to an 'alpha-ketobutyrate oxidase'.
    Medline: 11104678
  4. K. Tittmann et al. (1998), J. Biol. Chem., 273, 12929-12934. Activation of thiamin diphosphate and FAD in the phosphate dependent pyruvate oxidase from Lactobacillus plantarum.
    Medline: 9582325

Homologue information for M0275 (3ey9)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ

GOA logo
magnesium ion binding (molecular function)
catalytic activity (molecular function)
transferase activity (molecular function)
thiamine pyrophosphate binding (molecular function)
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