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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1996-1-26
|
| pubmed:abstractText |
Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of dopamine. Recently, we described a point mutation in hTH (Q381K) in a family of two siblings suffering from progressive L-DOPA-responsive dystonia (DRD), representing the first reported mutation in this gene. We here describe the cloning, expression and steady-state kinetic properties of the recombinant mutant enzyme. When expressed by a coupled in vitro transcription-translation system and in E. coli, the mutant enzyme represents a kinetic variant form, with a reduced affinity for L-tyrosine. The 'residual activity' of about 15% of the corresponding wild-type hTH (isoform hTH1), at substrate concentrations prevailing in vivo, is compatible with the clinical phenotype of the two Q381K homozygote patients carrying this recessively inherited mutation.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0964-6906
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
4
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1209-12
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8528210-Animals,
pubmed-meshheading:8528210-Base Sequence,
pubmed-meshheading:8528210-Codon,
pubmed-meshheading:8528210-Dystonia,
pubmed-meshheading:8528210-Escherichia coli,
pubmed-meshheading:8528210-Genes, Recessive,
pubmed-meshheading:8528210-Homozygote,
pubmed-meshheading:8528210-Humans,
pubmed-meshheading:8528210-Levodopa,
pubmed-meshheading:8528210-Molecular Sequence Data,
pubmed-meshheading:8528210-Mutagenesis, Site-Directed,
pubmed-meshheading:8528210-Phenotype,
pubmed-meshheading:8528210-Point Mutation,
pubmed-meshheading:8528210-Polymerase Chain Reaction,
pubmed-meshheading:8528210-Protein Biosynthesis,
pubmed-meshheading:8528210-Rabbits,
pubmed-meshheading:8528210-Recombinant Proteins,
pubmed-meshheading:8528210-Transcription, Genetic,
pubmed-meshheading:8528210-Tyrosine 3-Monooxygenase
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene.
|
| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, University of Bergen, Norway.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|