Overview for MACiE Entry M0146
EC Number: 188.8.131.52 (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:
"Other" CATH Codes:
Display structure information
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 . The role served by Tyr404A could also be served by Cys557A.
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Stepwise Description of the Reaction
|Step 1||His144 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 2||Asp174 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 3||Tyr404 deprotonates the second substrate (1,2,3,5-tetrahydroxybenzene) at the C2-OH position.|
|Step 4||The 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 5||Water deprotonates the C5 position of the original substrate, resulting in double bond isomerisation.|
|Step 6||Water 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 7||The 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 8||Mo(IV) donates a single electron into the bound quinone, resulting in the protonation of the ketone group at the 2 position from Asp174.|
|Step 9||Mo(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
||Location of Function
Metal Cofactors for M0146
- 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.
- R. Hille et al. (1999), FEMS Microbiol. Rev., 22, 489-501. Mechanistic aspects of molybdenum-containing enzymes.
Homologue information for M0146 (1ti6)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
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