DB code: D00478

CATH domain -.-.-.- :
1.10.800.10 : Phenylalanine Hydroxylase Catalytic domain
E.C. 1.14.16.2
CSA 2toh
M-CSA 2toh
MACiE M0134

CATH domain Related DB codes (homologues)
1.10.800.10 : Phenylalanine Hydroxylase D00496

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P04177 Tyrosine 3-monooxygenase
EC 1.14.16.2
Tyrosine 3-hydroxylase
TH
NP_036872.1 (Protein)
NM_012740.3 (DNA/RNA sequence)
PF00351 (Biopterin_H)
PF12549 (TOH_N)
[Graphical View]

KEGG enzyme name
tyrosine 3-monooxygenase
L-tyrosine hydroxylase
tyrosine 3-hydroxylase
tyrosine hydroxylase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P04177 TY3H_RAT L-tyrosine + tetrahydrobiopterin + O(2) = 3,4- dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin. Homotetramer. Fe(2+) ion.

KEGG Pathways
Map code Pathways E.C.
MAP00350 Tyrosine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00023 C00082 C00272 C00007 C00355 C15522
E.C.
Compound Iron L-Tyrosine Tetrahydrobiopterin O2 3,4-Dihydroxy-L-phenylalanine 4a-hydroxytetrahydrobiopterin
Type heavy metal amino acids,aromatic ring (only carbon atom) amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate others amino acids,aromatic ring (only carbon atom) amine group,aromatic ring (with nitrogen atoms),carbohydrate
ChEBI 18248
 82664
 18248
 82664
 		17895
 58315
 17895
 58315
 		59560
 59560
 		15379
 26689
 27140
 15379
 26689
 27140
 		15765
 57504
 15765
 57504
PubChem 23925
 23925
 		6057
 6942100
 6057
 6942100
 		44257
 44257
 		977
 977
 		6047
 6971033
 6047
 6971033
 		46173804
 46173804
1tohA Bound:_FE Unbound Unbound Unbound Unbound Unbound
2tohA Bound:_FE Unbound Analogue:HBI Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Swiss-prot;P04177

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1tohA HIS 331;HIS 336;GLU 376(Iron binding)
2tohA HIS 331;HIS 336;GLU 376(Iron binding) MTY 300(Self-hydroxylated)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[5]
p.580-581
[6]
Scheme 1, p.13444
[12]
Scheme 2, p.2085-2087
[13]
Fig. 6, p.1071-1073

References
[1]
Resource
Comments
Medline ID
PubMed ID 1979980
Journal J Biol Chem
Year 1990
Volume 265
Pages 22358-64
Authors Mitchell JP, Hardie DG, Vulliet PR
Title Site-specific phosphorylation of tyrosine hydroxylase after KCl depolarization and nerve growth factor treatment of PC12 cells.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 8105857
Journal J Mol Neurosci
Year 1993
Volume 4
Pages 125-39
Authors Ribeiro P, Wang Y, Citron BA, Kaufman S
Title Deletion mutagenesis of rat PC12 tyrosine hydroxylase regulatory and catalytic domains.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 7964718
Journal J Neurochem
Year 1994
Volume 63
Pages 2014-20
Authors Vrana KE, Walker SJ, Rucker P, Liu X
Title A carboxyl terminal leucine zipper is required for tyrosine hydroxylase tetramer formation.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8535244
Journal Protein Sci
Year 1995
Volume 4
Pages 2082-6
Authors Ramsey AJ, Daubner SC, Ehrlich JI, Fitzpatrick PF
Title Identification of iron ligands in tyrosine hydroxylase by mutagenesis of conserved histidinyl residues.
Related PDB
Related UniProtKB
[5]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 164-498
Medline ID 97372896
PubMed ID 9228951
Journal Nat Struct Biol
Year 1997
Volume 4
Pages 578-85
Authors Goodwill KE, Sabatier C, Marks C, Raag R, Fitzpatrick PF, Stevens RC
Title Crystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases.
Related PDB 1toh
Related UniProtKB P04177
[6]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 9753429
Journal Biochemistry
Year 1998
Volume 37
Pages 13437-45
Authors Goodwill KE, Sabatier C, Stevens RC
Title Crystal structure of tyrosine hydroxylase with bound cofactor analogue and iron at 2.3 A resolution: self-hydroxylation of Phe300 and the pterin-binding site.
Related PDB 2toh
Related UniProtKB P04177
[7]
Resource
Comments
Medline ID
PubMed ID 9589369
Journal J Mol Neurosci
Year 1998
Volume 10
Pages 45-51
Authors Mockus SM, Yohrling GJ 4th, Vrana KE
Title Tyrosine hydroxylase and tryptophan hydroxylase do not form heterotetramers.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11076506
Journal Biochemistry
Year 2000
Volume 39
Pages 13676-86
Authors Almas B, Toska K, Teigen K, Groehn V, Pfleiderer W, Martinez A, Flatmark T, Haavik J
Title A kinetic and conformational study on the interaction of tetrahydropteridines with tyrosine hydroxylase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 10900078
Journal J Neurosci Res
Year 2000
Volume 61
Pages 313-20
Authors Yohrling GJ 4th, Jiang GC, Mockus SM, Vrana KE
Title Intersubunit binding domains within tyrosine hydroxylase and tryptophan hydroxylase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 11401575
Journal Biochemistry
Year 2001
Volume 40
Pages 7273-8
Authors McCulloch RI, Daubner SC, Fitzpatrick PF
Title Effects of substitution at serine 40 of tyrosine hydroxylase on catecholamine binding.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 12361946
Journal J Biol Chem
Year 2002
Volume 277
Pages 47653-61
Authors Stultz CM, Levin AD, Edelman ER
Title Phosphorylation-induced conformational changes in a mitogen-activated protein kinase substrate. Implications for tyrosine hydroxylase activation.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 12590596
Journal Biochemistry
Year 2003
Volume 42
Pages 2081-8
Authors Fitzpatrick PF, Ralph EC, Ellis HR, Willmon OJ, Daubner SC
Title Characterization of metal ligand mutants of tyrosine hydroxylase: insights into the plasticity of a 2-histidine-1-carboxylate triad.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 12631267
Journal Eur J Biochem
Year 2003
Volume 270
Pages 1065-75
Authors Maass A, Scholz J, Moser A
Title Modeled ligand-protein complexes elucidate the origin of substrate specificity and provide insight into catalytic mechanisms of phenylalanine hydroxylase and tyrosine hydroxylase.
Related PDB
Related UniProtKB

Comments
The structure of the N-terminal domain of this enzyme has not been determined yet.

Created Updated
2004-01-27 2009-02-26