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Overview for MACiE Entry M0274

Version history

General Information

EC Number: 1.2.3.3 (A member of the Oxidoreductases, Acting on the aldehyde or oxo group of donors, With oxygen as acceptor)

Enzyme Name: pyruvate oxidase

Biological Species: Lactobacillus plantarum (Lactobacillus plantarum)

Catalytic Chain UniprotKB Accession Codes:

Representative PDB Code: 1pow - THE REFINED STRUCTURES OF A STABILIZED MUTANT AND OF WILD-TYPEPYRUVATE OXIDASE FROM LACTOBACILLUS PLANTARUM (Resolution = 2.50 Å).

Catalytic CATH Codes:

Display structure information

Overall Reaction:

Image of oxygen

Image of phosphate

Image of proton

Image of pyruvate

right arrow

Image of carbon dioxide

Image of acetyl phosphate

Image of hydrogen peroxide

oxygen
C00007
CHEBI:15379
phosphate
C00009
CHEBI:18367
proton
C00080
CHEBI:24636
pyruvate
C00022
CHEBI:15361
carbon dioxide
C00011
CHEBI:16526
acetyl phosphate
C00227
CHEBI:13711
hydrogen peroxide
C00027
CHEBI:16240

Overall Comment: An alternative mechanism involving a transient radical cation has been proposed based on the same evidence present in the cited references.


View similar reactions


Stepwise Description of the Reaction

Step 1Glu59' 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 Glu59'.
Step 3The covalently bound pyruvate undergoes decarboxylation.
Step 4A single electron is transferred from the high energy thamine diphosphate enamine intermediate to the FAD, resulting in bond order rearrangement and deprotonation of the alcohol group present on the intermediate.
Step 5Tautomerisation of the resulting radical intermediate.
Step 6The thiamine ring nitrogen acts as an electron sink in the formation of the radical tautomer.
Step 7Phosphate initiates a nucleophilic attack on the kinetically stable anion radical adduct.
Step 8The high energy phosphate radical delivers a second reducing equivalent to the FAD semiquinone.
Step 9The tetrahedral anion intermediate collapses. This forms the high energy metabolite acetyl-phosphate.
Step 10The FAD diradical transfers one of its electrons to dioxygen with subsequent loss of a single proton.
Step 11The FADH transfers the second radical and proton to the dioxygen to regenerate the FAD cofactor and hydrogen peroxide.
Step 12The TTP cofactor is regenerated by reprotonation of the C2 position.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Val 394 A Side Chain
Gln 122 A Side Chain
Phe 479 A Side Chain
Ile 480 A Side Chain
Glu 59 B Side Chain
Phe 121 A Side Chain

Organic Cofactors for M0274

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

Metal Cofactors for M0274

Type Het group Number Chain
magnesium MG 610 A Overview

References

  1. K. Tittmann et al. (2000), Biochemistry, 39, 10747-10754. Mechanism of elementary catalytic steps of pyruvate oxidase from Lacobacillus plantarum.
    Medline: 10978159
  2. G. Wille et al. (0), Biochemistry, 44, 5086-5094. .
    Medline: 15794646
  3. G. Wille et al. (2006), Nat. Chem. Biol., 2, 324-328. The catalytic role of a thiamin diphosphate enzyme examined by crystallography.
    Medline: 16680160
  4. K. Tittmann et al. (2009), FEBS Journal, 276, 2454-2468. Reaction mechanisms of thiamin diphosphate enzymes: redox reactions.
    Medline: 19476487
  5. Y. A. Muller et al. (1994), J. Mol. Biol., 237, 315-335. The refined structures of a stabilized mutant and of wild-type pyruvate oxidase from Lactobacillus plantarum.
    Medline: 8145244
  6. 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 M0274 (1pow)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0106 pyruvate dehydrogenase (acetyl-transferring)
1.2.4.1
1w85 3.40.50.970
0.59250.0752Compare
M0280 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)
1.2.4.4
1dtw 3.40.50.970
0.59250.0776Compare
M0119 pyruvate:ferredoxin oxidoreducatse
1.2.7.1
2c3m 3.40.50.970
0.6470.0871Compare
M0219 transketolase
2.2.1.1
1trk 3.40.50.970
0.8820.0706Compare
M0289 acetolactate synthase
2.2.1.6
1n0h 3.40.50.970
0.57850.2122Compare
M0215 pyruvate decarboxylase
4.1.1.1
1pvd 3.40.50.970
0.90110.1265Compare
M0220 benzoylformate decarboxylase
4.1.1.7
1mcz 3.40.50.970
0.74610.1223Compare
M0221 benzoin aldolase
4.1.2.38
2ag0 3.40.50.970
0.78350.1882Compare

View a comparison of the other reactions in MACiE with the CATH domain 3.40.50.970


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
Link to EzCatDB

GOA logo
magnesium ion binding (molecular function)
catalytic activity (molecular function)
oxidoreductase activity (molecular function)
transferase activity (molecular function)
thiamine pyrophosphate binding (molecular function)
metal ion binding (molecular function)
pyruvate oxidase activity (molecular function)
oxidation-reduction process (biological process)
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