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Overview for MACiE Entry M0146

Version history

General Information

EC Number: 1.97.1.2 (A member of the Oxidoreductases, Other oxidoreductases, Sole sub-subclass for oxidoreductases that do not belong in the other subclasses)

Enzyme Name: pyrogallol hydroxytransferase

Biological Species: Pelobacter acidigallici (Bacteria)

Catalytic Chain UniprotKB Accession Codes:

  • P80563 - Pyrogallol hydroxytransferase large subunit

Representative PDB Code: 1ti6 - CRYSTAL STRUCTURE OF PYROGALLOL-PHLOROGLUCINOLTRANSHYDROXYLASE FROM PELOBACTER ACIDIGALLICI COMPLEXEDWITH INHIBITOR 1,2,4,5-TETRAHYDROXY-BENZENE (Resolution = 2.00 Å).

Catalytic CATH Codes:

  • Unassigned Domain

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of 1,2,3,5-tetrahydroxybenzene

Image of pyrogallol

right arrow

Image of phloroglucinol

Image of 1,2,3,5-tetrahydroxybenzene

1,2,3,5-tetrahydroxybenzene
C03743
CHEBI:16746
pyrogallol
C01108
CHEBI:16164
phloroglucinol
C02183
CHEBI:16204
1,2,3,5-tetrahydroxybenzene
C03743
CHEBI:16746

Overall Comment: There are three alternative proposals for the catalytic mechanism. Two mechanisms function without co-substrate involve a rotation of the substrate in the active site and the transferred hydroxyl stems from the solvent. The mechanism shown here includes 1,2,3,5-tetrahydroxybenzene as co-substrate through a diphenylether intermediate and therefore the transferred hydroxyl does not originate from solvent. The 3D structure of the enzyme supports the participation of a co-substrate [1]. The role served by Tyr404A could also be served by Cys557A.


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Stepwise Description of the Reaction

Step 1His144 deprotonates the pyrogallol substrate at the C3-OH position, the activated substrate then attacks the molybdenum cofactor in a nucleophilic substitution, resulting in the loss of a water molecule from the Mo(VI) coordination sphere.
Step 2Asp174 deprotonates the bound intermediate at the C2-OH position, resulting in a isomerisation to form the diquinone form of the substrate, and a two electron reduction of the molybdenum cofactor resulting in an Mo(IV) oxidation state.
Step 3Tyr404 deprotonates the second substrate (1,2,3,5-tetrahydroxybenzene) at the C2-OH position.
Step 4The activated 1,2,3,5-tetrahydroxybenzene then attacks the Mo-coordinated intermediate in a nucleophilic addition, which is reprotonated from His144 at the C2=O position.
Step 5Water deprotonates the C5 position of the original substrate, resulting in double bond isomerisation.
Step 6Water deprotonates the C5 hydroxyl of the original 1,2,3,5-tetrahydroxybenzene molecule, resulting in double bond isomerisations that lead to the protonation of the C2 position of the original 1,2,3,5-tetrahydroxybenzene molecule from water.
Step 7The negatively charged oxygen at the 2 position of the original pyrogallol substrate initiates an elimination reaction which produces the diquinone form of 1,2,3,5-tetrahydroxybenzene (this is the molecule that was pyrogallol) and the product phloroglucinol from the molecule that was 1,2,3,5-tetrahydroxybenzene
Step 8Mo(IV) donates a single electron into the bound quinone, resulting in the protonation of the ketone group at the 2 position from Asp174.
Step 9Mo(V) donates a second electron to the bound quinone, causing the ketone at the 5 position to protonate from Tyr404. The 1,2,3,5-tetrahydroxybenzene is displaced from the molybdenum's coordination sphere by water.

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Catalytic Residues Involved

Type Number Chain Location of Function
His 144 A Side Chain
Asp 174 A Side Chain
Tyr 404 A Side Chain

Metal Cofactors for M0146

Type Het group Number Chain
molybdenum 4MO 902 A Overview

References

  1. A. Messerschmidt et al. (2004), Proc. Natl Acad. Sci. USA, 101, 11571-11576. Crystal structure of pyrogallol-phloroglucinol transhydroxylase, an Mo enzyme capable of intermolecular hydroxyl transfer between phenols.
    Medline: 15284442
  2. R. Hille et al. (1999), FEMS Microbiol. Rev., 22, 489-501. Mechanistic aspects of molybdenum-containing enzymes.
    Medline: 10189201

Homologue information for M0146 (1ti6)

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
binding (molecular function)
oxidoreductase activity (molecular function)
pyrogallol hydroxytransferase activity (molecular function)
molybdenum ion binding (molecular function)
metal ion binding (molecular function)
oxidation-reduction process (biological process)
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