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Mutational Analysis of Substrate Inhibition in Tyrosine Hydroxylase
Author(s) -
Quinsey Noelene S.,
Luong Anh Q.,
Dickson Phillip W.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71052132.x
Subject(s) - mutant , mutagenesis , substrate (aquarium) , allosteric regulation , tyrosine hydroxylase , tyrosine , mutation , chemistry , saturated mutagenesis , biochemistry , enzyme , substrate specificity , biology , microbiology and biotechnology , genetics , gene , ecology
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 Trp 166 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.