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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 2toh

E.C. nametyrosine 3-monooxygenase
SpeciesRattus norvegicus (Rat)
E.C. Number (IntEnz) 1.14.16.2
CSA Homologues of 2toh
CSA Entries With UniProtID P04177
CSA Entries With EC Number 1.14.16.2
PDBe Entry 2toh
PDBSum Entry 2toh
MACiE Entry M0134

Literature Report

IntroductionTyrosine hydroxylase, sourced from Rattus norvegicus belongs to a family of pterin-dependent monooxygenases. It catalyses the hydroxylation of the aromatic group of tyrosine. Tyrosine hydroxylase is found in the central nervous system and the adrenal gland where it's role is to catalyse the production of dihydroxyphenylalanine (DOPA) - the rate limiting step in the biosynthesis of catecholamine neurotransmitters.
Mechansim1. Fe(II) binds to the oxygen molecule, to give Fe(II)O2. This undergoes an irreversible step involving single electron transfer from pterin to the oxygen to form Fe(II)O2- and a pterin cation radical. 2. Radical collapse occurs and intermediate Fe(II) u-peroxypterin is formed. Heterolytic cleavage of the O-O bond of the intermediate results in the hydroxypterin product and an electrophilic Fe(IV)O species. The Fe(IV)O species is stabilised by ligand His 331. His 331 is stabilised electrostatically by Ser 395. 3. Electrophilic aromatic substitution takes place. The aromatic ring of tyrosine becomes hydroxylated.
Reaction

Catalytic Sites for 2toh

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
SerA395395macie:sideChainSer 395 electrostatically stabilises His 331.
HisA331331macie:sideChainHis 331 stabilises the Fe(IV)O species.

Literature References

Notes:
Fitzpatrick PF.
Mechanism of aromatic amino acid hydroxylation.
Biochemistry 2003 42 14083-14091
PubMed: 14640675
Ellis HR
Mutation of serine 395 of tyrosine hydroxylase decouples oxygen-oxygen bond cleavage and tyrosine hydroxylation.
Biochemistry 2000 39 4174-4181
PubMed: 10747809
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