The 2.0 Å crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals a fold similar to that of tyrosine hydroxylase. It provides the first structural view of where mutations occur and a rationale to explain molecular mechanisms of the enzymatic phenotypes in the autosomal recessive disorder phenylketoneuria.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Structure of full-length wild-type human phenylalanine hydroxylase by small angle X-ray scattering reveals substrate-induced conformational stability
Scientific Reports Open Access 20 September 2019
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Kaufman, S. Adv. Enz. 67, 67–77 (1993).
Hoang, L., Byck, S., Prevost, L., Scriver, C.R. Nucleic Acid Res. 24, 127–131 (1996).
Scriver, C.R., Kaufman, S., Eisensmith, R.C., Woo, S.L.C. In The metabolic basis of inherited disease (eds Scriver, C.R., Beaudet, A.L., Sly, W.S. and Valle, D.) 1015–1075 (McGraw Hill, New York; 1995).
Erlandsen, H., Martinez, A., Knappskog, P.M., Haavik, J., Hough, E., Flatmark, T. FEBS Lett. 406, 171–174 (1997).
Knappskog, P.M., Flatmark, T., Aarden, J.M., Haavik, J., Martinez, A. Eur. J. Biochem. 242, 813–821 (1996).
Goodwill, K.E., Sabatier, C., Marks, C., Raag, R., Fitzpatrick, P.F., Stevens, R.C. Nature Struct. Biol. 4, 578–585 (1997).
Kabsch, W. and Sander, C. Biopolymers 22, 2577–2637 (1983).
Martinez, A., Andersson, K.K., Haavik, J., Flatmark, T. Eur. J. Biochem. 198, 675–682 (1991).
Gibbs, B.S., Wojchowski, D., Benkovic, S.J. J. Biol, Chem. 268, 8046–8052 (1993).
Kappock, T.J., Caradonna, J.P. Chem. Rev. 96, 2659–2756 (1996).
Martinez, A., Olafsdottir, S., Flatmark, T. Eur. J. Biochem. 211, 259–266 (1993).
Hufton, S.E., Jennings, I.G., Cotton, G.H. Biochem. J. 311, 353–366 (1995); Jennings, I.G., Kemp, B.E., Cotton, R.G.H. Proc. Natl. Acad. Sci. USA 88, 5734–5738 (1991).
Ayling, J.E., Boehm, G.R., Textor, S.C., Pirson, R.A. Biochemistry 12, 2045–2051 (1973).
Almås, B., Groehn, V., Flatmark, T., Pfleiderer, W., Haavik, J. Pteridines 8, 137–138 (1997).
Almås, B., Le Bourdelles, B., Flatmark, T., Mallet, J., Haavik, J. Eur. J. Biochem. 209, 249–255 (1992).
Martinez, A., Haavik, J., Flatmark, T. Eur. J. Biochem. 193, 211–219 (1990).
Han, S., Eltis, L.D., Timmis, K.N., Muchmore, S.W., Bolin, J.T. Science 270, 976–980 (1996); Senda, T., Sugiyama, K., Narita, H., Yamamoto, T., Kimbara, K., Fukuda, M., Sato, M., Yano, K., Mitsui, Y. J. Mol. Biol. 255, 735–752 (1996).
Okano, Y., Eisensmith, R.C., Guttler, F., Lichter-Konecki, U., Konecki, D.S., Trefz, F.K., Dasovich, M., Wang, T., Henriksen, K., Lou, H., Woo, S.L.C. New Eng. J. Med. 324, 1232–1238.
Fiatmark, T., Knappskog, P.M., Bjørgo, E., Martinez, A. in Chemistry and biology of pteridines and folates (eds Pfleiderer, H. and Rokos, H.) 503–508 (Blackwell Science, London; 1997).
Baric, L., Mardesic, D., Sarnavoka, V., Lichter-Konecki, U., Konecki, D.S., Trefz, F.K. J. Inherit. Metab. Dis. 17, 376–377 (1994).
Okano, Y., Wang, T., Eisensmith, R.C., Longhi, R., Riva, E., Giovannini, M., Cerone, R., Romano, C., Woo, S.L.C. Genomics 9, 96–103 (1991).
Knappskog, P.M., Eiken, H.G., Martinez, A., Olafsdottir, S., Haavik, J., Flatmark, T., Apold, J. Adv. fxper. Med. Biol. 338, 59–62 (1993).
Marvit, J., DiLella, A.G., Brayton, K., Ledley, F.D., Robson, K.J.H., Woo, S.L.C. Nucleic Acids Res. 15, 5613–5628 (1987).
DiLella, A.G., Marvit, J., Brayton, K., Woo, S.L.C. Nature 327, 333–336 (1987).
Svensson, E., Eisensmith, R.C., Dworniczak, B., von Dobeln, U., Hagenfeldt, L., Horst, J., Woo, S.L.C. Hum. Mutat. 1, 129–137 (1992).
Otwinowski Z., (1998), DENZO. A program for automatic film evaluation of film intensities. Yale University, New Haven, CT.
Navaza, J. Acta Crystallogr., A50, 157–163 (1994).
Brunger A. T., XPLOR Version 3.1. A system for Crystallography and NMR. Yale University Press, New Haven, CT (1992).
CCP4: A suite of programs for Protein Crystallography (SERC Daresbury Laboratory, Warrington, WA4 4AD, UK (1979).
Collaborative Computational Project, Number 4, Acta Crystallogr., D 50, 760–763 (1994).
Bhat, T.N J. Appl. Crystallogr., 21, 279–281 (1988).
Hodel, A., Kim, S.-H., Brunger, A.T. Acta Crystallogr. A 48, 851–859 (1992).
Jones, T.A., Zou, J. Y, Cowans, S.W. and Kjeldgaard, M. Acta Crystallogr., A47, 110–119 (1991).
Colovos, C., Yeates, T.O. Prot. Sci. 2, 1511–1519 (1993).
Laskowski, R. A., MacArthus, M. W., Moss, D. S., Thornton, J. M. J. Appl. Crystallogr. 26, 283–291 (1993).
Vriend, G. J. Mol. Graph. 8, 52–56 (1990).
Kraulis, P. J. J. Appl. Crystallogr., 24, 946–950 (1991).
Merritt, E. A., Murphy, M. E. P. Acta Crystallogr., D 50, 869–873 (1994).
Nicholls, A. GRASP: Graphical Representation and Analysis of Surface Properties, Columbia University, New York.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Erlandsen, H., Fusetti, F., Martinez, A. et al. Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria. Nat Struct Mol Biol 4, 995–1000 (1997). https://doi.org/10.1038/nsb1297-995
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nsb1297-995
This article is cited by
-
Structure of full-length wild-type human phenylalanine hydroxylase by small angle X-ray scattering reveals substrate-induced conformational stability
Scientific Reports (2019)
-
Computational study of missense mutations in phenylalanine hydroxylase
Journal of Molecular Modeling (2015)
-
Studies on a new dinuclear CoII–pterin complex exhibiting reactivity towards phenylalanine and bromobenzene
Transition Metal Chemistry (2007)
-
Effects and clinical significance of tetrahydrobiopterin supplementation in phenylalanine hydroxylase‐deficient hyperphenylalaninaemia
Journal of Inherited Metabolic Disease (2007)
-
Biochemical Conservation of Recombinant Drosophila Tyrosine Hydroxylase with its Mammalian Cognates
Biochemical Genetics (2005)