Mutational analysis of substrate inhibition in tyrosine hydroxylase.
J Neurochem
; 71(5): 2132-8, 1998 Nov.
Article
em En
| MEDLINE
| ID: mdl-9798939
ABSTRACT
Substrate inhibition in tyrosine hydroxylase (TH) was analyzed by deletion mutagenesis. The deletion mutant TH 156/456 was the smallest section of TH to retain substrate inhibition. The TH 156/456 was monomeric, and so multimer formation does not play a role in substrate inhibition in TH. Further deletion at the N terminus to residue 169 produced a TH molecule with no substrate inhibition but high activity. A mutagenic scan of this region showed that mutations at Trp166 were responsible for this phenotype. A screen of a library of TH molecules containing random mutations identified three other mutants that had lost substrate inhibition but retained high activity. The results in this report are consistent with a model in which substrate inhibition acts through an allosteric mechanism.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tirosina 3-Mono-Oxigenase
/
Análise Mutacional de DNA
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Austrália