TY - JOUR
T1 - Structural insights into the regulation of aromatic amino acid hydroxylation
AU - Fitzpatrick, Paul F.
N1 - Funding Information:
The research described here from the author's laboratory was supported by grants from the National Institutes of Health ( GM047291 and GM098140 ).
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - The aromatic amino acid hydroxylases phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase are homotetramers, with each subunit containing a homologous catalytic domain and a divergent regulatory domain. The solution structure of the regulatory domain of tyrosine hydroxylase establishes that it contains a core ACT domain similar to that in phenylalanine hydroxylase. The isolated regulatory domain of tyrosine hydroxylase forms a stable dimer, while that of phenylalanine hydroxylase undergoes a monomer-dimer equilibrium, with phenylalanine stabilizing the dimer. These solution properties are consistent with the regulatory mechanisms of the two enzymes, in that phenylalanine hydroxylase is activated by phenylalanine binding to an allosteric site, while tyrosine hydroxylase is regulated by binding of catecholamines in the active site.
AB - The aromatic amino acid hydroxylases phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylase are homotetramers, with each subunit containing a homologous catalytic domain and a divergent regulatory domain. The solution structure of the regulatory domain of tyrosine hydroxylase establishes that it contains a core ACT domain similar to that in phenylalanine hydroxylase. The isolated regulatory domain of tyrosine hydroxylase forms a stable dimer, while that of phenylalanine hydroxylase undergoes a monomer-dimer equilibrium, with phenylalanine stabilizing the dimer. These solution properties are consistent with the regulatory mechanisms of the two enzymes, in that phenylalanine hydroxylase is activated by phenylalanine binding to an allosteric site, while tyrosine hydroxylase is regulated by binding of catecholamines in the active site.
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U2 - 10.1016/j.sbi.2015.07.004
DO - 10.1016/j.sbi.2015.07.004
M3 - Review article
C2 - 26241318
AN - SCOPUS:84938295263
VL - 35
SP - 1
EP - 6
JO - Current Opinion in Structural Biology
JF - Current Opinion in Structural Biology
SN - 0959-440X
ER -