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Overview for MACiE Entry M0298

Version history

General Information

EC Number: 4.1.1.47 (A member of the Lyases, Carbon-carbon lyases, Carboxy-lyases)

Enzyme Name: tartronate-semialdehyde synthase

Biological Species: Escherichia coli (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P0AEP7 - Glyoxylate carboligase

Representative PDB Code: 2pan - CRYSTAL STRUCTURE OF E. COLI GLYOXYLATE CARBOLIGASE (Resolution = 2.70 Å).

Catalytic CATH Codes:

  • Unassigned Domain

Display structure information

Overall Reaction:

Image of glyoxylate

Image of proton

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Image of carbon dioxide

Image of 2-hydroxy-3-oxopropanoate

2 glyoxylate
C00048
CHEBI:36655
proton
C00080
CHEBI:24636
carbon dioxide
C00011
CHEBI:16526
2-hydroxy-3-oxopropanoate
C01146
CHEBI:57978

Overall Comment: This enzyme utilizes a thiamine diphosphate cofactor to catalyse the condensation reaction between two molecules of glyoxylate. The mechanism, however, does not begin with a proton transfer to a conserved gluatmate, as is the case for every other enzyme that uses this cofactor. Instead, the aliphatic residues surrounding the cofactor act to lower the dielectric constant of the active site, leading to activation of the cofactor by intramolecular proton rearrangement.


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Stepwise Description of the Reaction

Step 1The cofactor undergoes an intramolecular proton transfer between the pyrimidine and thiazole ring, forming a carbon-nitrogen ylid.
Step 2The carbanion of thiamine diphosphate initiates a nucleophilic attack on the carbonyl carbon of glyoxylate in an addition reaction. The conjugated double bond system of the cofactor undergoes rearrangement.
Step 3The glyoxylate-TDP adduct undergoes decarboxylation with concomitant bond rearrangement on the thiazole ring.
Step 4The nitrogen of the thiazole ring initiates conjugate nucleophilic attack at the carbonyl of the second glyoxylate molecule, with inferred, concomitant, intramolecular proton rearrangement.
Step 5The oxyanion initiates elimination, forming the single S enantiomer of 2-Hydroxy-3-oxopropanoate and regenerating the activated form of the thiamine diphosphate cofactor.
Step 6Protonation at the C2 position regenerates the thiamine diphosphate cofactor, and the enzyme active site.

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Catalytic Residues Involved

Type Number Chain Location of Function
Val 51 A Side Chain
Leu 421 A Side Chain
Leu 476 A Side Chain
Ile 479 A Side Chain
Val 25 A Side Chain

Organic Cofactors for M0298

Type Identity Chain
Thiamine diphosphate TDP 801 A Overview

Metal Cofactors for M0298

Type Het group Number Chain
magnesium MG 851 A Overview

References

  1. A. Kaplun et al. (2008), Nat. Chem. Biol., 4, 113-118. Glyoxylate carboligase lacks the canonical active site glutamate of thiamine-dependent enzymes.
    Medline: 18176558
  2. B. Shaanan et al. (2009), FEBS Journal, 276, 2447-2253. Reaction mechanisms of thiamin diphosphate enzymes: new insights into the role of a conserved glutamate residue.
    Medline: 19476486
  3. S. Zhang et al. (2004), J. Biol. Chem., 279, 54312-54318. C2-alpha-lactylthiamin diphosphate is an intermediate on the pathway of thiamin diphosphate-dependent pyruvate decarboxylation. Evidence on enzymes and models.
    Medline: 15501823
  4. S. Zhang et al. (2005), Biochemistry, 44, 2237-2243. Evidence for dramatic acceleration of a C-H bond ionization rate in thiamin diphosphate enzymes by the protein environment.
    Medline: 15709735

Homologue information for M0298 (2pan)

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)
tartronate-semialdehyde synthase activity (molecular function)
glyoxylate catabolic process (biological process)
thiamine pyrophosphate binding (molecular function)
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