PMID- 15135070
OWN - NLM
STAT- MEDLINE
DCOM- 20040623
LR  - 20131121
IS  - 0014-5793 (Print)
IS  - 0014-5793 (Linking)
VI  - 565
IP  - 1-3
DP  - 2004 May 7
TI  - Different stabilities and denaturation pathways for structurally related aromatic 
      amino acid hydroxylases.
PG  - 155-9
AB  - 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.
FAU - Kleppe, Rune
AU  - Kleppe R
AD  - Department of Biomedicine, Division for Anatomy and Cell Biology, University of 
      Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway.
FAU - Haavik, Jan
AU  - Haavik J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Protein Isoforms)
RN  - 8W8T17847W (Urea)
RN  - EC 1.14.16.1 (Phenylalanine Hydroxylase)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
SB  - IM
MH  - Circular Dichroism
MH  - Dimerization
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - Light
MH  - Mutation, Missense
MH  - Phenylalanine Hydroxylase/*chemistry
MH  - Protein Binding
MH  - Protein Denaturation
MH  - Protein Isoforms
MH  - Protein Structure, Secondary
MH  - Scattering, Radiation
MH  - Spectrometry, Fluorescence
MH  - Time Factors
MH  - Tryptophan Hydroxylase/*chemistry
MH  - Tyrosine 3-Monooxygenase/*chemistry
MH  - Urea/pharmacology
EDAT- 2004/05/12 05:00
MHDA- 2004/06/24 05:00
CRDT- 2004/05/12 05:00
PHST- 2004/02/26 00:00 [received]
PHST- 2004/03/29 00:00 [revised]
PHST- 2004/03/29 00:00 [accepted]
PHST- 2004/05/12 05:00 [pubmed]
PHST- 2004/06/24 05:00 [medline]
PHST- 2004/05/12 05:00 [entrez]
AID - S0014579304004132 [pii]
AID - 10.1016/j.febslet.2004.03.092 [doi]
PST - ppublish
SO  - FEBS Lett. 2004 May 7;565(1-3):155-9. doi: 10.1016/j.febslet.2004.03.092.