EzCatDB: D00478
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DB codeD00478
CATH domainDomain 1-.-.-.-
Domain 21.10.800.10 : Phenylalanine HydroxylaseCatalytic domain
E.C.1.14.16.2
CSA2toh
MACiEM0134

CATH domainRelated DB codes (homologues)
1.10.800.10 : Phenylalanine HydroxylaseD00496

Enzyme Name
UniProtKBKEGG

P04177
Protein nameTyrosine 3-monooxygenasetyrosine 3-monooxygenase
L-tyrosine hydroxylase
tyrosine 3-hydroxylase
tyrosine hydroxylase
SynonymsEC 1.14.16.2
Tyrosine 3-hydroxylase
TH
RefSeqNP_036872.1 (Protein)
NM_012740.3 (DNA/RNA sequence)
PfamPF00351 (Biopterin_H)
PF12549 (TOH_N)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00350Tyrosine metabolism

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

Compound table: links to PDB-related databases & PoSSuM

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
ChEBI18248
82664
17895
58315
59560
27140
26689
15379
15765
57504

PubChem23925
6942100
6057
44257
977
6971033
6047
46173804
              
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 UniProtKBP04177
[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 UniProtKBP04177
[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


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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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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