EzCatDB: D00478

DB codeD00478
CATH domainDomain 1-.-.-.-
Domain 21.10.800.10Catalytic domain
E.C.1.14.16.2
CSA2toh
MACiEM0134

CATH domainRelated DB codes (homologues)
1.10.800.10D00496

Enzyme Name
Swiss-protKEGG

P04177
Protein nameTyrosine 3-monooxygenasetyrosine 3-monooxygenase
L-tyrosine hydroxylase
tyrosine 3-hydroxylase
tyrosine hydroxylase
SynonymsEC 1.14.16.2
Tyrosine 3-hydroxylase
TH

KEGG pathways
MAP codePathways
MAP00350Tyrosine metabolism

Swiss-prot:Accession NumberP04177
Entry nameTY3H_RAT
ActivityL-tyrosine + tetrahydrobiopterin + O(2) = 3,4- dihydroxy-L-phenylalanine + 4a-hydroxytetrahydrobiopterin.
SubunitHomotetramer.
Subcellular location
CofactorFe(2+) ion.


CofactorsSubstratesProducts
KEGG-idC00023C00082C00272C00007C00355C15522
CompoundIronL-TyrosineTetrahydrobiopterinO23,4-Dihydroxy-L-phenylalanine4a-hydroxytetrahydrobiopterin
Typeheavy metalamino acids,aromatic ring (only carbon atom)amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrateothersamino acids,aromatic ring (only carbon atom)amine group,aromatic ring (with nitrogen atoms),carbohydrate
1tohABound:_FEUnboundUnboundUnboundUnboundUnbound
2tohABound:_FEUnboundAnalogue:HBIUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P04177
pdbCofactor-binding residuesModified residues
1tohAHIS 331;HIS 336;GLU 376(Iron binding)

2tohAHIS 331;HIS 336;GLU 376(Iron binding)
MTY 300(Self-hydroxylated)

References for Catalytic Mechanism
ReferencesSectionsNo. 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]
PubMed ID1979980
JournalJ Biol Chem
Year1990
Volume265
Pages22358-64
AuthorsMitchell JP, Hardie DG, Vulliet PR
TitleSite-specific phosphorylation of tyrosine hydroxylase after KCl depolarization and nerve growth factor treatment of PC12 cells.
[2]
PubMed ID8105857
JournalJ Mol Neurosci
Year1993
Volume4
Pages125-39
AuthorsRibeiro P, Wang Y, Citron BA, Kaufman S
TitleDeletion mutagenesis of rat PC12 tyrosine hydroxylase regulatory and catalytic domains.
[3]
PubMed ID7964718
JournalJ Neurochem
Year1994
Volume63
Pages2014-20
AuthorsVrana KE, Walker SJ, Rucker P, Liu X
TitleA carboxyl terminal leucine zipper is required for tyrosine hydroxylase tetramer formation.
[4]
PubMed ID8535244
JournalProtein Sci
Year1995
Volume4
Pages2082-6
AuthorsRamsey AJ, Daubner SC, Ehrlich JI, Fitzpatrick PF
TitleIdentification of iron ligands in tyrosine hydroxylase by mutagenesis of conserved histidinyl residues.
[5]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 164-498
Medline ID97372896
PubMed ID9228951
JournalNat Struct Biol
Year1997
Volume4
Pages578-85
AuthorsGoodwill KE, Sabatier C, Marks C, Raag R, Fitzpatrick PF, Stevens RC
TitleCrystal structure of tyrosine hydroxylase at 2.3 A and its implications for inherited neurodegenerative diseases.
Related PDB1toh
Related Swiss-protP04177
[6]
CommentsX-ray crystallography
PubMed ID9753429
JournalBiochemistry
Year1998
Volume37
Pages13437-45
AuthorsGoodwill KE, Sabatier C, Stevens RC
TitleCrystal 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 PDB2toh
Related Swiss-protP04177
[7]
PubMed ID9589369
JournalJ Mol Neurosci
Year1998
Volume10
Pages45-51
AuthorsMockus SM, Yohrling GJ 4th, Vrana KE
TitleTyrosine hydroxylase and tryptophan hydroxylase do not form heterotetramers.
[8]
PubMed ID11076506
JournalBiochemistry
Year2000
Volume39
Pages13676-86
AuthorsAlmas B, Toska K, Teigen K, Groehn V, Pfleiderer W, Martinez A, Flatmark T, Haavik J
TitleA kinetic and conformational study on the interaction of tetrahydropteridines with tyrosine hydroxylase.
[9]
PubMed ID10900078
JournalJ Neurosci Res
Year2000
Volume61
Pages313-20
AuthorsYohrling GJ 4th, Jiang GC, Mockus SM, Vrana KE
TitleIntersubunit binding domains within tyrosine hydroxylase and tryptophan hydroxylase.
[10]
PubMed ID11401575
JournalBiochemistry
Year2001
Volume40
Pages7273-8
AuthorsMcCulloch RI, Daubner SC, Fitzpatrick PF
TitleEffects of substitution at serine 40 of tyrosine hydroxylase on catecholamine binding.
[11]
PubMed ID12361946
JournalJ Biol Chem
Year2002
Volume277
Pages47653-61
AuthorsStultz CM, Levin AD, Edelman ER
TitlePhosphorylation-induced conformational changes in a mitogen-activated protein kinase substrate. Implications for tyrosine hydroxylase activation.
[12]
PubMed ID12590596
JournalBiochemistry
Year2003
Volume42
Pages2081-8
AuthorsFitzpatrick PF, Ralph EC, Ellis HR, Willmon OJ, Daubner SC
TitleCharacterization of metal ligand mutants of tyrosine hydroxylase: insights into the plasticity of a 2-histidine-1-carboxylate triad.
[13]
PubMed ID12631267
JournalEur J Biochem
Year2003
Volume270
Pages1065-75
AuthorsMaass A, Scholz J, Moser A
TitleModeled ligand-protein complexes elucidate the origin of substrate specificity and provide insight into catalytic mechanisms of phenylalanine hydroxylase and tyrosine hydroxylase.

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

createdupdated
2004-01-272009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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