Towards the identification of the allosteric Phe-binding site in phenylalanine hydroxylase

Journal of Biomolecular Structure and Dynamics

Volumn 34, Issue 3, 2016, Pages 497-507

  Carluccio, Carla ^a   Fraternali, Franca ^b   Salvatore, Francesco ^a,c   Fornili, Arianna ^b   Zagari, Adriana ^a  

^a CEINGE BIOTECNOLOGIE AVANZATE   (Italy)

^b KING'S COLLEGE LONDON   (United Kingdom)

^c IRCCS SDN   (Italy)

Author keywords

allosteric Phe binding site; hPAH p.G46S mutation; hyperphenylalaninemia; molecular docking simulations; molecular dynamics simulations

Indexed keywords

PHENYLALANINE; PHENYLALANINE 4 MONOOXYGENASE; PROTEIN BINDING;

ALLOSTERISM; ARTICLE; BINDING SITE; CATALYSIS; CONTROLLED STUDY; DIMERIZATION; MOLECULAR DOCKING; MOLECULAR DYNAMICS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DOMAIN; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; WILD TYPE; CHEMISTRY; ENZYME ACTIVE SITE; GENETICS; HUMAN; METABOLISM; MOLECULAR MODEL; MUTATION; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION;

ALLOSTERIC REGULATION; ALLOSTERIC SITE; BINDING SITES; CATALYTIC DOMAIN; HUMANS; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; MOLECULAR DYNAMICS SIMULATION; MUTATION; PHENYLALANINE; PHENYLALANINE HYDROXYLASE; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN MULTIMERIZATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84962422623     PISSN: 07391102     EISSN: 15380254     Source Type: Journal    
DOI: 10.1080/07391102.2015.1052016     Document Type: Article

References (38)

1. Aravind, L., &, Koonin, E. V. (1999). Gleaning non-trivial structural, functional and evolutionary information about proteins by iterative database searches. Journal of Molecular Biology, 287, 1023-1040. 10.1006/jmbi.1999.2653
2. Berendsen, H. J. C., Postma, J. P. M., van Gunsteren, W. F., &, Hermans, J. (1981). Interaction models for water in relation to protein hydration. In B. Pullman. (Ed.), Intermolecular forces (pp. 331-342). Dordrecht, NL: Springer-Science+Business Media. 10.1007/978-94-015-7658-1
3. Bjørgo, E., de Carvalho, R. M., &, Flatmark, T. (2001). A comparison of kinetic and regulatory properties of the tetrameric and dimeric forms of wild-type and Thr427->Pro mutant human phenylalanine hydroxylase. European Journal of Biochemistry, 268, 997-1005. 10.1046/j.1432-1327.2001.01958.x
4. Carluccio, C., Fraternali, F., Salvatore, F., Fornili, A., &, Zagari, A. (2013). Structural features of the regulatory ACT domain of phenylalanine hydroxylase. PLoS ONE, 8, e79482. 10.1371/journal.pone.0079482
5. Cerreto, M., Cavaliere, P., Carluccio, C., Amato, F., Zagari, A., Daniele, A., &, Salvatore, F. (2011). Natural phenylalanine hydroxylase variants that confer a mild phenotype affect the enzymes conformational stability and oligomerization equilibrium. Biochimica et Biophysica Acta (BBA) -Molecular Basis of Disease, 1812, 1435-1445. 10.1016/j.bbadis.2011.07.012
6. Chemical Computing Group Inc. (2012). Molecular Operating Environment (MOE), 2012.10. 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7.
7. Corbeil, C. R., Williams, C. I., &, Labute, P. (2012). Variability in docking success rates due to dataset preparation. Journal of Computer-Aided Molecular Design, 26, 775-786. 10.1007/s10822-012-9570-1
8. Daniele, A., Cardillo, G., Pennino, C., Carbone, M. T., Scognamiglio, D., Esposito, L., &, Correra, A. (2008). Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1782, 378-384. 10.1016/j.bbadis.2008.01.012
9. Daniele, A., Scala, I., Cardillo, G., Pennino, C., Ungaro, C., Sibilio, M., &, Parenti, G. (2009). Functional and structural characterization of novel mutations and genotype-phenotype correlation in 51 phenylalanine hydroxylase deficient families from Southern Italy. FEBS Journal, 276, 2048-2059. 10.1111/j.1742-4658.2009.06940.x
10. Døskeland, A. P., Martínez, A., Knappskog, P. M., &, Flatmark, T. (1996). Phosphorylation of recombinant human phenylalanine hydroxylase: Effect on catalytic activity, substrate activation and protection against nonspecific cleavage of the fusion protein by restriction protease. Biochemical Journal, 313, 409-414.
11. Erlandsen, H., &, Stevens, R. C. (1999). The structural basis of phenylketonuria. Molecular Genetics and Metabolism, 68, 103-125. 10.1006/mgme.1999.2922
12. Fitzpatrick, P. F. (2000). The aromatic amino acid hydroxylases. Advances in Enzymology and Related Areas of Molecular Biology, 74, 235-294.
13. Fitzpatrick, P. F. (2012). Allosteric regulation of phenylalanine hydroxylase. Archives of Biochemistry and Biophysics, 519, 194-201. 10.1016/j.abb.2011.09.012
14. Flatmark, T., &, Stevens, R. C. (1999). Structural insight into the aromatic amino acid hydroxylases and their disease-related mutant forms. Chemical Reviews, 99, 2137-2160. 10.1021/cr980450y
15. Gersting, S., Kemter, K., Staudigl, M., Messing, D., Danecka, M., Lagler, F., &, Sommerhoff, C. P. (2008). Loss of function in phenylketonuria is caused by impaired molecular motions and conformational instability. The American Journal of Human Genetics, 83, 5-17. 10.1016/j.ajhg.2008.05.013
16. Gjetting, T., Petersen, M., Guldberg, P., &, Güttler, F. (2001). Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine. The American Journal of Human Genetics, 68, 1353-1360. 10.1086/320604
17. Grant, G. A. (2006). The ACT domain: A small molecule binding domain and its role as a common regulatory element. Journal of Biological Chemistry, 281, 33825-33829. 10.1074/jbc.R600024200
18. Hufton, S. E., Jennings, I. G., &, Cotton, R. G. (1998). Structure/function analysis of the domains required for the multimerisation of phenylalanine hydroxylase. Biochimica et Biophysica Acta (BBA)-Protein Structure and Molecular Enzymology, 1382, 295-304. 10.1016/S0167-4838(97)00171-4
19. Jaffe, E. K., Stith, L., Lawrence, S. H., Andrake, M., &, Dunbrack, R. L. J. (2013). A new model for allosteric regulation of phenylalanine hydroxylase: Implications for disease and therapeutics. Archives of Biochemistry and Biophysics, 530, 73-82. 10.1016/j.abb.2012.12.017
20. Kaufman, S. (1993). The phenylalanine hydroxylating system. Advances Enzymology, 70, 77-264.
21. Knappskog, P. M., Flatmark, T., Aarden, J. M., Haavik, J., &, Martinez, A. (1996). Structure/function relationships in human phenylalanine hydroxylase. Effect of terminal deletions on the oligomerization, activation and cooperativity of substrate binding to the enzyme. European Journal of Biochemistry, 242, 813-821. 10.1111/ejb.1996.242.issue-3
22. Kobe, B., Jennings, I. G., House, C. M., Michell, B. J., Goodwill, K. E., Santarsiero, B. D.,., Kemp, B. E. (1999). Structural basis of autoregulation of phenylalanine hydroxylase. Nature Structural Biology, 6, 442-448. 10.1038/8247
23. Leandro, J., Simonsen, N., Saraste, J., Leandro, P., &, Flatmark, T. (2011). Phenylketonuria as a protein misfolding disease: The mutation pG46S in phenylalanine hydroxylase promotes self-association and fibril formation. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1812, 106-120. 10.1016/j.bbadis.2010.09.015
24. Lehtonen, J., Still, D., Rantanen, V., Ekholm, J., Björklund, D., Iftikhar, Z., &, Huhtala, M. (2004). BODIL: A molecular modeling environment for structure-function analysis and drug design. Journal of Computer-Aided Molecular Design, 18, 401-419. 10.1007/s10822-004-3752-4
25. Li, J., Dangott, L. J., &, Fitzpatrick, P. F. (2010). Regulation of phenylalanine hydroxylase: Conformational changes upon phenylalanine binding detected by hydrogen/deuterium exchange and mass spectrometry. Biochemistry, 49, 3327-3335. 10.1021/bi1001294
26. Li, J., Ilangovan, U., Daubner, S. C., Hinck, A. P., &, Fitzpatrick, P. F. (2011). Direct evidence for a phenylalanine site in the regulatory domain of phenylalanine hydroxylase. Archives of Biochemistry and Biophysics, 505, 250-255. 10.1016/j.abb.2010.10.009
27. Martínez, A., Knappskog, P. M., Olafsdottir, S., Døskeland, A. P., Eiken, H. G., Svebak, R. M., &, Flatmark, T. (1995). Expression of recombinant human phenylalanine hydroxylase as fusion protein in Escherichia coli circumvents proteolytic degradation by host cell proteases. Isolation and characterization of the wild-type enzyme. Biochemistry Journal, 306, 589-597.
28. Pey, A., Stricher, F., Serrano, L., &, Martinez, A. (2007). Predicted effects of missense mutations on native-state stability account for phenotypic outcome in phenylketonuria, a paradigm of misfolding diseases. The American Journal of Human Genetics, 81, 1006-1024. 10.1086/521879
29. Roberts, K. M., Khan, C. A., Hinck, C. S., &, Fitzpatrick, P. F. (2014). Activation of phenylalanine hydroxylase by phenylalanine does not require binding in the active site. Biochemistry, 53, 7846-7853. 10.1021/bi501183x
30. Šali, A., &, Blundell, T. L. (1993). Comparative protein modelling by satisfaction of spatial restraints. Journal of Molecular Biology, 234, 779-815. 10.1006/jmbi.1993.1626
31. Shiman, R., &, Gray, D. W. (1980). Substrate activation of phenylalanine hydroxylase. A kineic characterization, Journal of Biological Chemistry, 255, 4793-4800.
32. Shiman, R., Jones, S. H., &, Gray, D. W. (1990). Mechanism of phenylalanine regulation of phenylalanine hydroxylase. Journal of Biological Chemistry, 265, 11633-11642.
33. Tan, K., Li, H., Zhang, R., Gu, M., Clancy, S. T., &, Joachimiak, A. (2008). Structures of open (R) and close (T) states of prephenate dehydratase (PDT)-Implication of allosteric regulation by l-phenylalanine. Journal of Structural Biology, 162, 94-107. 10.1016/j.jsb.2007.11.009
34. Thórólfsson, M., Ibarra-Molero, B., Fojan, P., Petersen, S. B., Sanchez-Ruiz, J. M., &, Martínez, A. (2002). l-Phenylalanine binding and domain organization in human phenylalanine hydroxylase: A differential scanning calorimetry study. Biochemistry, 41, 7573-7585. 10.1021/bi0160720
35. Vallian, S., Barahimi, E., &, Moeini, H. (2003). Phenylketonuria in Iranian population: A study in institutions for mentally retarded in Isfahan. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 526, 45-52. 10.1016/S0027-5107(03)00015-0
36. Van Der Spoel, D., Lindahl, E., Hess, B., Groenhof, G., Mark, A. E., &, Berendsen, H. J. C. (2005). GROMACS: Fast, flexible, and free. Journal of Computational Chemistry, 26, 1701-1718. 10.1002/(ISSN)1096-987X
37. van Gunsteren, W. F., Billeter, S. R., Eising, A. A., Hünenberger, P. H., Krüger, P., Mark, A. E., &, Tironi, I. G. (1996). Biomolecular simulation: The GROMOS96 manual and userguide. Zürich: Hochschuleverlag AG an der ETH Zürich.
38. Zhang, S., Roberts, K. M., &, Fitzpatrick, P. F. (2014). Phenylalanine binding is linked to dimerization of the regulatory domain of phenylalanine hydroxylase. Biochemistry, 53, 6625-6627. 10.1021/bi501109s