Different stabilities and denaturation pathways for structurally related aromatic amino acid hydroxylases.

Abstract:

:We have compared the urea stability of the human aromatic amino acid hydroxylases (AAAHs), key enzymes involved in neurotransmitter biosynthesis and amino acid homeostasis. Tyrosine-, tryptophan- and phenylalanine hydroxylase (TH, TPH and PAH, respectively) were transiently activated at low urea concentrations and rapidly inactivated in >3 M urea. The denaturation of TH occurred through two cooperative transitions, with denaturation midpoints of 1.41+/-0.06 and 5.13+/-0.05 M urea, respectively. Partially denatured human TH (hTH) retained more of its secondary structure than human PAH (hPAH), and was found to exist as tetramers, whereas hPAH dissociated into dimers. Furthermore, the urea-induced aggregation of hPAH was 100-fold higher than for hTH. These results suggest that the denatured state properties of the AAAHs contribute significantly to the stability of these enzymes and their tolerance towards missense mutations.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Kleppe R,Haavik J

doi

10.1016/j.febslet.2004.03.092

keywords:

subject

Has Abstract

pub_date

2004-05-07 00:00:00

pages

155-9

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S0014579304004132

journal_volume

565

pub_type

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