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Human pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1 alpha

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1995

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Köster, Sandra
Thöny, Beat
Macheroux, Peter
Curtius, Hans-Christoph
Heizmann, Claus W.

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European Journal of Biochemistry. 1995, 231(2), pp. 414-423. ISSN 0014-2956. eISSN 1432-1033

Zusammenfassung

Pterin-4a-carbinolamine dehydratase/dimerization cofactor for hepatocyte nuclear factor-1α is a protein with two different functions. We have overexpressed and purified the human wild-type protein, and its Cys81Ser and Cys81Arg mutants. The Cys81Arg mutant has been proposed to be causative in a hyperphenylalaninaemic patient [Citron, B. A., Kaufman, S., Milstien, S., Naylor, E. W., Greene, C. L. & Davis, M. D. (1993) Am. J. Hum. Genet. 53, 768 774]. The dehydratase behaves as a tetramer on gel filtration, while cross-linking experiments showed mono-, di-, tri-, and tetrameric forms, irrespective of the presence of the single Cys81. Sulfhydryl-modifying reagents did not affect the activity, but rather showed that Cys81 is exposed. Various pterins bind and quench the tryptophan fluorescence suggesting the presence of a specific binding site. The fluorescence is destroyed upon light irradiation. Wild-type and the Cys81Ser protein enhance the rate of the phenylalanine hydroxylase assay ≈ 10-fold, a value similar to that of native dehydratase from rat liver; the Cys81Arg mutant, in contrast, has significantly lower activity. This is compatible with the hypothesis that the dehydratase is a rate-limiting factor for the in vivo phenylalanine hydroxylase reaction. The three proteins enhance the spontaneous dehydration of the synthetic substrate 6,6-dimethyl-7,8-dihydropterin-4a-carbinolamine ≈50 70-fold at 4°C and pH 8.5. The results are discussed in view of the recently solved three-dimensional structure of the enzyme [Ficner, R., Sauer, U. W., Stier, G. & Suck, D. (1995) EMBO J. 14, 2032 2042].

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Fachgebiet (DDC)
570 Biowissenschaften, Biologie

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Pterin-4a-carbinolamine, dehydratase, phenylalanine hydroxylase, tetrahydrobiopterin, hepatocyte nuclear factor-1α

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ISO 690KÖSTER, Sandra, Beat THÖNY, Peter MACHEROUX, Hans-Christoph CURTIUS, Claus W. HEIZMANN, Wolfgang PFLEIDERER, Sandro GHISLA, 1995. Human pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1 alpha. In: European Journal of Biochemistry. 1995, 231(2), pp. 414-423. ISSN 0014-2956. eISSN 1432-1033
BibTex
@article{Koster1995Human-7375,
  year={1995},
  title={Human pterin-4 alpha-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1 alpha},
  number={2},
  volume={231},
  issn={0014-2956},
  journal={European Journal of Biochemistry},
  pages={414--423},
  author={Köster, Sandra and Thöny, Beat and Macheroux, Peter and Curtius, Hans-Christoph and Heizmann, Claus W. and Pfleiderer, Wolfgang and Ghisla, Sandro}
}
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