Tyrosine hydroxylase
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| Tyrosine hydroxylase
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| PDB | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Available structures: For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format).
The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free. HistoryFounded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB). The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community. The PDB is a key resource in structural biology and is critical to more recent work in structural genomics. Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution. GrowthWhen the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off. The growth rate of the PDB has been the subject of fairly extensive analysis. ContentsAs of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose. Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used. StatisticsAs of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:
Note that theoretical models are no longer accepted in the PDB. 22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file. The current breakdown of holdings is updated weekly. File formatThrough the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.
This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects; The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons. Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs. If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction). Various funding agencies and scientific journals now require scientists to submit their structure data to PDB. Viewing the dataThe structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software. ReferencesPrinted
Online
Other external links
Links to enzyme database data
Molecular graphic visualisation tools
The Protein Data Bank (PDB) is a repository for 3-D structural data of proteins and nucleic acids. These data, typically obtained by X-ray crystallography or NMR spectroscopy, are submitted by biologists and biochemists from around the world, are released into the public domain, and can be accessed for free. HistoryFounded in 1971 by Drs. Edgar Meyer and Walter Hamilton Brookhaven National Laboratory, management of the Protein Data Bank was transferred in 1998 to members of the Research Collaboratory for Structural Bioinformatics (RCSB). The Worldwide Protein Data Bank (wwPDB) consists of organizations that act as deposition, data processing and distribution centers for PDB data. The founding members are RCSB PDB (USA), MSD-EBI (Europe) and PDBj (Japan). The BMRB (USA) group joined the wwPDB in 2006. The mission of the wwPDB is to maintain a single Protein Data Bank Archive of macromolecular structural data that is freely and publicly available to the global community. The PDB is a key resource in structural biology and is critical to more recent work in structural genomics. Countless derived databases and projects have been developed to integrate and classify the PDB in terms of protein structure, protein function and protein evolution. GrowthWhen the PDB was originally founded it contained just 7 protein structures. Since then it has undergone an approximate exponential growth in the number of structures, which does not show any sign of falling off. The growth rate of the PDB has been the subject of fairly extensive analysis. ContentsAs of 26 September, 2006, the database contained 39,051 released atomic coordinate entries (or "structures"), 35,767 of that proteins, the rest being nucleic acids, nucleic acid-protein complexes, and a few other molecules. About 5,000 new structures are released each year. Data are stored in the mmCIF format specifically developed for the purpose. Note that the database stores information about the exact location of all atoms in a large biomolecule (although, usually without the hydrogen atoms, as their positions are more of a statistical estimate); if one is only interested in sequence data, i.e. the list of amino acids making up a particular protein or the list of nucleotides making up a particular nucleic acid, the much larger databases from Swiss-Prot and the International Nucleotide Sequence Database Collaboration should be used. StatisticsAs of 11 September, 2007, the "PDB Holdings List" at RCSB reported the following statistics:
Note that theoretical models are no longer accepted in the PDB. 22461 structures in the PDB have a structure factor file. 3138 structures in the PDB have an NMR restraint file. The current breakdown of holdings is updated weekly. File formatThrough the years the PDB file format has undergone many, many changes and revisions. Its original format was dictated by the width of computer punch cards.
This legacy format has caused many problems with the format, and consequently there are 'clean-up' projects; The MMDB uses ASN.1 (and an XML conversion of this format). The wwPDB members RCSB PDB, MSD-EBI, and PDBj are working together to make the data uniform across the archive. Some believe this to be desirable; others argue that, without a universal repository of information (i.e., a common dictionary), it is not possible to draw comparisons. Each structure published in PDB receives a four-character alphanumeric identifier, its PDB ID. This should not be used as an identifier for biomolecules, since often several structures for the same molecule (in different environments or conformations) are contained in PDB with different PDB IDs. If a biologist submits structure data for a protein or nucleic acid, wwPDB staff reviews and annotates the entry. The data are then automatically checked for plausibility. The source code for this validation software has been released for free. The main data base accepts only experimentally derived structures, and not theoretically predicted ones (see protein structure prediction). Various funding agencies and scientific journals now require scientists to submit their structure data to PDB. Viewing the dataThe structural data can be used to visualize the biomolecules with appropriate software, such as VMD, RasMol, PyMOL, Jmol, MDL Chime, QuteMol, web browser VRML plugin or any web-based software designed to visualize and analyse the protein structures such as STING. A recent desktop software addition is Sirius. The RCSB PDB website also contains resources for education, structural genomics, and related software. ReferencesPrinted
Online
Other external links
Links to enzyme database data
Molecular graphic visualisation tools
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| Identifiers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Symbol(s) | TH; TYH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 191290 MGI: 98735 Homologene: 307 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| EC number | 1.14.16.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| RNA expression pattern | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Human | Mouse | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Entrez | 7054 | 21823 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ensembl | ENSG00000180176 | ENSMUSG00000000214 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Uniprot | P07101 | Q3UTB3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Refseq | NM_000360 (mRNA) NP_000351 (protein) | NM_009377 (mRNA) NP_033403 (protein) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Location | Chr 11: 2.14 - 2.15 Mb | Chr 7: 142.7 - 142.71 Mb | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pubmed search | [9] | [10] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to dihydroxyphenylalanine (DOPA). DOPA is a precursor for dopamine which in turn is a precursor for norepinephrine (noradrenaline) and epinephrine (adrenaline).
The enzyme, an oxygenase, is found in the cytosol of all cells containing catecholamines. This initial reaction is the rate limiting step in the production of catecholamines.
The enzyme is highly specific, not accepting indole derivatives - which is unusual as many other enzymes involved in the production of catecholamines do.
Clinical significance
Tyrosine hydroxylase can be inhibited by the drug α-methyl tyrosine (Metirosine), however it is not an effective means of regulating noradrenaline synthesis. This drug is rarely used, but it is useful in treating pheochromocytoma and also resistant hypertension.
Tyrosine hydroxylase is an autoantigen in Autoimmune Polyendocrine Syndrome (APS) type I.
References
- Pharmacology 5th Ed, by Rang, Dale Ritter and Moore
- Biochemical and Biophysical Communications 267, 456-461 (2000) Identification of tyrosine hydroxylase as an autoantigen in autoimmune polyendocrine syndrome type I
Further reading
- Masserano JM, Weiner N (1983). "Tyrosine hydroxylase regulation in the central nervous system.". Mol. Cell. Biochem. 53-54 (1-2): 129-52. PMID 6137760.
- Meloni R, Biguet NF, Mallet J (2002). "Post-genomic era and gene discovery for psychiatric diseases: there is a new art of the trade? The example of the HUMTH01 microsatellite in the Tyrosine Hydroxylase gene.". Mol. Neurobiol. 26 (2-3): 389-403. PMID 12428766.
- Joh TH, Park DH, Reis DJ (1979). "Direct phosphorylation of brain tyrosine hydroxylase by cyclic AMP-dependent protein kinase: mechanism of enzyme activation.". Proc. Natl. Acad. Sci. U.S.A. 75 (10): 4744-8. PMID 33381.
- Haycock JW, Ahn NG, Cobb MH, Krebs EG (1992). "ERK1 and ERK2, two microtubule-associated protein 2 kinases, mediate the phosphorylation of tyrosine hydroxylase at serine-31 in situ.". Proc. Natl. Acad. Sci. U.S.A. 89 (6): 2365-9. PMID 1347949.
- Haycock JW (1990). "Phosphorylation of tyrosine hydroxylase in situ at serine 8, 19, 31, and 40.". J. Biol. Chem. 265 (20): 11682-91. PMID 1973163.
- Craig SP, Buckle VJ, Lamouroux A, et al. (1986). "Localization of the human tyrosine hydroxylase gene to 11p15: gene duplication and evolution of metabolic pathways.". Cytogenet. Cell Genet. 42 (1-2): 29-32. PMID 2872999.
- Grima B, Lamouroux A, Boni C, et al. (1987). "A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics.". Nature 326 (6114): 707-11. doi:10.1038/326707a0. PMID 2882428.
- Kaneda N, Kobayashi K, Ichinose H, et al. (1987). "Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene.". Biochem. Biophys. Res. Commun. 146 (3): 971-5. PMID 2887169.
- Kobayashi K, Kaneda N, Ichinose H, et al. (1987). "Isolation of a full-length cDNA clone encoding human tyrosine hydroxylase type 3.". Nucleic Acids Res. 15 (16): 6733. PMID 2888085.
- O'Malley KL, Anhalt MJ, Martin BM, et al. (1988). "Isolation and characterization of the human tyrosine hydroxylase gene: identification of 5' alternative splice sites responsible for multiple mRNAs.". Biochemistry 26 (22): 6910-4. PMID 2892528.
- Le Bourdellès B, Boularand S, Boni C, et al. (1988). "Analysis of the 5' region of the human tyrosine hydroxylase gene: combinatorial patterns of exon splicing generate multiple regulated tyrosine hydroxylase isoforms.". J. Neurochem. 50 (3): 988-91. PMID 2892893.
- Ginns EI, Rehavi M, Martin BM, et al. (1988). "Expression of human tyrosine hydroxylase cDNA in invertebrate cells using a baculovirus vector.". J. Biol. Chem. 263 (15): 7406-10. PMID 2896667.
- Kobayashi K, Kaneda N, Ichinose H, et al. (1988). "Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types.". J. Biochem. 103 (6): 907-12. PMID 2902075.
- Coker GT, Vinnedge L, O'Malley KL (1989). "Characterization of rat and human tyrosine hydroxylase genes: functional expression of both promoters in neuronal and non-neuronal cell types.". Biochem. Biophys. Res. Commun. 157 (3): 1341-7. PMID 2905129.
- Vulliet PR, Woodgett JR, Cohen P (1984). "Phosphorylation of tyrosine hydroxylase by calmodulin-dependent multiprotein kinase.". J. Biol. Chem. 259 (22): 13680-3. PMID 6150037.
- Zhou QY, Quaife CJ, Palmiter RD (1995). "Targeted disruption of the tyrosine hydroxylase gene reveals that catecholamines are required for mouse fetal development.". Nature 374 (6523): 640-3. doi:10.1038/374640a0. PMID 7715703.
- Lüdecke B, Bartholomé K (1995). "Frequent sequence variant in the human tyrosine hydroxylase gene.". Hum. Genet. 95 (6): 716. PMID 7789962.
- Lüdecke B, Dworniczak B, Bartholomé K (1995). "A point mutation in the tyrosine hydroxylase gene associated with Segawa's syndrome.". Hum. Genet. 95 (1): 123-5. PMID 7814018.
- Knappskog PM, Flatmark T, Mallet J, et al. (1996). "Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene.". Hum. Mol. Genet. 4 (7): 1209-12. PMID 8528210.
External links
Carrier proteins, metalloproteins: iron-binding proteins | |
|---|---|
| heme | Ferritin (Bacterioferritin) - Lactoferrin - Transferrin |
| nonheme | Hemerythrin - Inositol oxygenase - Iron-sulfur protein - Lipoxygenase - Tyrosine hydroxylase |
Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14) | |
|---|---|
| 1.14.11 - 2-oxoglutarate | Prolyl hydroxylase - Lysyl hydroxylase |
| 1.14.13 - NADH or NADPH | Flavin-containing monooxygenase - Nitric oxide synthase - Cholesterol 7 alpha-hydroxylase - Methane monooxygenase - 3A4 -51A1 |
| 1.14.14 - reduced flavin or flavoprotein | 19A1 - 2D6 - 2E1 |
| 1.14.15 - reduced iron-sulfur protein | 11B1 - 11B2 - 11A1 |
| 1.14.16 - reduced pteridine | Phenylalanine hydroxylase - Tyrosine hydroxylase - Tryptophan hydroxylase |
| 1.14.17 - reduced ascorbate | Dopamine beta hydroxylase |
| 1.14.18-19 - other | Tyrosinase - Stearoyl-CoA desaturase-1 |
| 1.14.99 - miscellaneous | Cyclooxygenase - Heme oxygenase (HMOX1) - Squalene monooxygenase - 17A1 - 21A2 |
