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Overview for MACiE Entry M0134

Version history

General Information

EC Number: 1.14.16.2 (A member of the Oxidoreductases, Acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2, With reduced pteridine as one donor, and incorporation of one atom of oxygen into the other donor)

Enzyme Name: tyrosine 3-monooxygenase

Biological Species: Rattus norvegicus (Rat)

Catalytic Chain UniprotKB Accession Codes:

  • P04177 - Tyrosine 3-monooxygenase

Representative PDB Code: 2toh - TYROSINE HYDROXYLASE CATALYTIC AND TETRAMERIZATION DOMAINS FROM RAT (Resolution = 2.30 Å).

Catalytic CATH Codes:

Display structure information

Overall Reaction:

Image of L-tyrosine

Image of oxygen

Image of tetrahydrobiopterin

right arrow

Image of 4a-hydroxytetrahydrobiopterin

Image of 3,4-dihydroxy-L-phenylalanine (L-dopa)

L-tyrosine
C00082
CHEBI:17895
oxygen
C00007
CHEBI:15379
tetrahydrobiopterin
C00272
CHEBI:59560
4a-hydroxytetrahydrobiopterin
C15522
CHEBI:15374
3,4-dihydroxy-L-phenylalanine (L-dopa)
C00355
CHEBI:15765

This reaction is irreversible.


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Stepwise Description of the Reaction

Step 1The Fe(II) centre donates a single electron to the dioxygen molecule in a homolytic addition.
Step 2The bound dioxygen radical initiates an electrophilic addition to the aromatic tetrahydrobiopterin which causes a single electron to be transferred back to the Fe(III) centre.
Step 3The Fe(II) centre donates an electron pair to the oxygen bound directly to the Fe ion, eliminating the 4a-hydroxytetrahydrobiopterin product by cleaving the peroxo bond. The product undergoes an internal proton transfer to generate the final state.
Step 4Tyrosine initiates an electrophilic addition to the bound iron-bound oxo group, causing the iron centre to accept two electrons.
Step 5In an NIH shift, the alkoxide group forms a ketone group, initiating an internal hydride transfer.
Step 6The intermediate undergoes a keto-enol tautomerisation forming the 3,4-dihydroxy-L-phenylalanine tautomer of the product.

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Catalytic Residues Involved

Type Number Chain Location of Function
His 331 A Side Chain
Ser 395 A Side Chain

Metal Cofactors for M0134

Type Het group Number Chain
iron FE 501 x Overview

References

  1. P. F. Fitzpatrick (2003), Biochemistry, 42, 14083-14091. Mechanism of aromatic amino acid hydroxylation.
    Medline: 14640675
  2. H. R. Ellis et al. (2000), Biochemistry, 39, 4174-4181. Mutation of serine 395 of tyrosine hydroxylase decouples oxygen-oxygen bond cleavage and tyrosine hydroxylation.
    Medline: 10747809

Homologue information for M0134 (2toh)

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
Link to EzCatDB

GOA logo
monooxygenase activity (molecular function)
iron ion binding (molecular function)
aromatic amino acid family metabolic process (biological process)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen (molecular function)
oxidation-reduction process (biological process)
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