Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants (358 views)
Bba-Gen Subjects (ISSN: 0925-4439, 0006-3002, 1570-9639), 2008 Jun; 1782(6): 378-384.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 2.233, 5-year impact factor: 2.816
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-43549124527&partnerID=40&md5=8844bbba125596993ff409c857bea650
Keywords: Expression Studies Of Pku Mutants, Pku Mutations, Pku Mutations Functional Analysis, Structural Analysis, Phenylalanine 4 Monooxygenase, Article, Controlled Study, Crystal Structure, Enzyme Activity, Gene Mutation, Human, Human Cell, Hyperphenylalaninemia, Italy, Loading Test, Pathogenesis, Phenotype, Priority Journal, Protein Analysis, Protein Expression, Reverse Transcription Polymerase Chain Reaction, Western Blotting, Cell Line, Dna Mutational Analysis, Genetic Predisposition To Disease, Models, Molecular, Phenylalanine Hydroxylase, Phenylketonurias, Protein Structure, Secondary, Reverse Transcriptase Polymerase Chain Reaction,
Affiliations:
*** IBB - CNR ***
CEINGE - Biotecnologie Avanzate Scarl, Via Comunale Margherita, 482, 80145 Naples, Italy
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini, 5, 80131 Naples, Italy
Dipartimento di Scienze per la Salute, Università del Molise, Via F. De Sanctis, 86100 Campobasso, Italy
Centro Screening Fenilchetonuria, Ospedale SS. Annunziata, ASL Na1, Via Egiziaca a Forcella, 18, 80139 Naples, Italy
CNR - Istituto di Biostrutture e Bioimmagini, Via Mezzocannone, 16, 80134 Naples, Italy
SEMM - European School of Molecular Medicine, Naples Site - CEINGE, Italy
References:
C.R. Scriver, S. Kaufman, The hyperphenylalaninemias, in: C.R. Scriver, A.L. Beaudet, S.W. Sly, D. Valle (eds) B. Childs, K.W. Kinzler, B. Vogelstein (assoc. eds), The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 2001, 8 ed., Ch. 77Scriver, C.R., The PAH gene, phenylketonuria, and a paradigm shift (2007) Hum. Mutat., 28, pp. 831-84
Scriver, C.R., Waters, P.J., Monogenic traits are not simple. Lessons from phenylketonuria (1999) Trends Genet., 15, pp. 267-272
Kaufman, S., Hyperphenylalaninaemia caused by defects in biopterin metabolism (1985) J. Inherit. Metab. Dis., 8 (SUPPL. 1), pp. 20-27
Leuzzi, V., Carducci, C., Carducci, C., Chiarotti, F., Artiola, C., Giovanniello, T., Antonozzi, I., The spectrum of phenylalanine variations under tetrahydrobiopterin load in subjects affected by phenylalanine hydroxylase deficiency (2006) J. Inherit. Metab. Dis., 29, pp. 38-46
Hennermann, J.B., Bührer, C., Blau, N., Vetter, B., Mönch, E., Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria (2005) Mol. Genet. Metab., 86, pp. S86-S90
Fiori, L., Fiege, B., Riva, E., Giovannini, M., Incidence of BH4-responsiveness in phenylalanine-hydroxylase-deficient Italian patients (2005) Mol. Genet. Metab., 86, pp. S67-S74
Fiege, B., Bonafe, L., Ballhausen, D., Baumgartner, M., Thony, B., Meili, D., Fiori, L., Blau, N., Extended tetrahydrobiopterin loading test in the diagnosis of cofactor-responsive phenylketonuria: a pilot study (2005) Mol. Genet. Metab., 86, pp. S91-S95
Levy, H.L., Milanowski, A., Chakrapani, A., Cleary, M., Lee, P., Trefz, F.K., Whitley, C.B., Dorenbaum, A., Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study (2007) Lancet, 370, pp. 504-510
Burton, B.K., Grange, D.K., Milanowski, A., Vockley, G., Feillet, F., Crombez, E.A., Abadie, V., Dorenbaum, A., The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study (2007) Inherit. Metab. Dis., 30, pp. 700-707
Scriver, C.R., Hurtubise, M., Konecki, D., Phommarinh, M., Prevost, L., Erlandsen, H., Stevens, R., Sarkissian, C., PAHdb 2003: what a locus-specific knowledgebase can do? (2003) Hum. Mutat., 21, pp. 333-344
Blau, N., Erlandsen, H., The metabolic and molecular bases of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency (2004) Mol. Genet. Metab., 82, pp. 101-111
Perez, B., Desviat, L.R., Gomez-Puertas, P., Martinez, A., Stevens, R.C., Ugarte, M., Kinetic and stability analysis of PKU mutations identified in BH4-responsive patients (2005) Mol. Genet. Metab., 86 (SUPPL. 1), pp. S11-S16
Waters, P.J., How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression (2003) Hum. Mutat., 21, pp. 357-369
Daniele, A., Cardillo, G., Pennino, C., Carbone, M.T., Scognamiglio, D., Correra, A., Pignero, A., Salvatore, F., Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: a 96% detection rate with ten novel mutations (2007) Ann. Hum. Genet., 71, pp. 185-193
Erlandsen, H., Fusetti, F., Martinez, A., Hough, E., Flatmark, T., Stevens, R.C., Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria (1997) Nat. Struct. Biol., 4, pp. 995-1000
Andersen, O.A., Flatmark, T., Hough, E., Crystal structure of the ternary complex of the catalytic domain of human phenylalanine hydroxylase with tetrahydrobiopterin and 3-(2-thienyl)-l-alanine, and its implications for the mechanism of catalysis and substrate activation (2002) J. Mol. Biol., 320, pp. 1095-1108
Andersen, O.A., Stokka, A.J., Flatmark, T., Hough, E., 2.0Å resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-l-alanine or l-norleucine: substrate specificity and molecular motions related to substrate binding (2003) J. Mol. Biol., 333, pp. 747-757
Kim, S.W., Jung, J., Oh, H.J., Kim, J., Lee, K.S., Lee, D.H., Park, C., Jung, S.C., Structural and functional analyses of mutations of the human phenylalanine hydroxylase gene (2006) Clin. Chim. Acta, 365, pp. 279-287
Erlandsen, H., Patch, M.G., Gamez, A., Straub, M., Stevens, R.C., Structural studies on phenylalanine hydroxylase and implications toward understanding and treating phenylketonuria (2003) Pediatrics, 112, pp. 1557-1565
Erlandsen, H., Pey, A.L., Gamez, A., Perez, B., Desviat, L.R., Aguado, C., Koch, R., Stevens, R.C., Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations (2004) Proc. Natl. Acad. Sci. U. S. A., 101, pp. 16903-16908
Daniele, A., Di Natale, P., Heparan N-sulfatase: cysteine 70 plays a role in the enzyme catalysis and processing (2001) FEBS Lett., 505, pp. 445-448
Mirisola, M.G., Calì, F., Gloria, A., Schinocca, P., D'Amato, M., Cassarà, G., Leo, G.D., Romano, V., PAH gene mutations in the Sicilian population: association with minihaplotypes and expression analysis (2001) Mol. Genet. Metab., 74, pp. 353-361
Bardelli, T., Donati, M.A., Gasperini, S., Ciani, F., Belli, F., Blau, N., Morrone, A., Zammarchi, E., Two novel genetic lesions and a common BH4-responsive mutation of the PAH gene in Italian patients with hyperphenylalaninemia (2002) Mol. Genet. Metab., 77, pp. 260-266
Muntau, A.C., Roschinger, W., Habich, M., Demmelmair, H.H., Hoffmann, B., Sommhoff, C.P., Roscher, A.A., Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria (2002) N. Engl. J. Med., 347, pp. 2122-2132
Pey, A.L., Perez, B., Desviat, L.R., Martinez, M.A., Aguado, C., Erlandsen, H., Gamez, A., Martinez, A., Mechanisms underlying responsiveness to tetrahydrobiopterin in mild phenylketonuria mutations (2004) Hum. Mutat., 24, pp. 388-399
Kure, S., Sato, K., Fujii, K., Aoki, Y., Suzuki, Y., Kato, S., Matsubara, Y., Wild-type phenylalanine hydroxylase activity is enhanced by tetrahydrobiopterin supplementation in vivo: an implication for therapeutic basis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency (2004) Mol. Genet. Metab., 83, pp. 150-156
Aguado, C., Perez, B., Ugarte, M., Desviat, L.R., Analysis of the effect of tetrahydrobiopterin on PAH gene expression in hepatoma cells (2006) FEBS Lett., 580, pp. 1697-1701
Giovannini, M., Verduci, E., Salvatici, E., Fiori, L., Riva, E., Phenylketonuria: dietary and therapeutic challenges (2007) J. Inherit. Metab. Dis., 30, pp. 145-152
Stokka, A.J., Carvalho, R.N., Barroso, J.F., Flatmark, T., Probing the role of crystallographically defined/predicted hinge-bending regions in the substrate-induced global conformational transition and catalytic activation of human phenylalanine hydroxylase by single-site mutagenesis (2004) J. Biol. Chem., 279, pp. 26571-26580
C. R. Scriver, S. Kaufman, The hyperphenylalaninemias, in: C. R. Scriver, A. L. Beaudet, S. W. Sly, D. Valle (eds) B. Childs, K. W. Kinzler, B. Vogelstein (assoc. eds), The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 2001, 8 ed., Ch. 77Scriver, C. R., The PAH gene, phenylketonuria, and a paradigm shift (2007) Hum. Mutat., 28, pp. 831-84
Scriver, C. R., Waters, P. J., Monogenic traits are not simple. Lessons from phenylketonuria (1999) Trends Genet., 15, pp. 267-272
Hennermann, J. B., B hrer, C., Blau, N., Vetter, B., M nch, E., Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria (2005) Mol. Genet. Metab., 86, pp. S86-S90
Levy, H. L., Milanowski, A., Chakrapani, A., Cleary, M., Lee, P., Trefz, F. K., Whitley, C. B., Dorenbaum, A., Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study (2007) Lancet, 370, pp. 504-510
Burton, B. K., Grange, D. K., Milanowski, A., Vockley, G., Feillet, F., Crombez, E. A., Abadie, V., Dorenbaum, A., The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study (2007) Inherit. Metab. Dis., 30, pp. 700-707
Scriver, C. R., Hurtubise, M., Konecki, D., Phommarinh, M., Prevost, L., Erlandsen, H., Stevens, R., Sarkissian, C., PAHdb 2003: what a locus-specific knowledgebase can do? (2003) Hum. Mutat., 21, pp. 333-344
Waters, P. J., How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression (2003) Hum. Mutat., 21, pp. 357-369
Andersen, O. A., Flatmark, T., Hough, E., Crystal structure of the ternary complex of the catalytic domain of human phenylalanine hydroxylase with tetrahydrobiopterin and 3- (2-thienyl) -l-alanine, and its implications for the mechanism of catalysis and substrate activation (2002) J. Mol. Biol., 320, pp. 1095-1108
Andersen, O. A., Stokka, A. J., Flatmark, T., Hough, E., 2. 0 resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3- (2-thienyl) -l-alanine or l-norleucine: substrate specificity and molecular motions related to substrate binding (2003) J. Mol. Biol., 333, pp. 747-757
Kim, S. W., Jung, J., Oh, H. J., Kim, J., Lee, K. S., Lee, D. H., Park, C., Jung, S. C., Structural and functional analyses of mutations of the human phenylalanine hydroxylase gene (2006) Clin. Chim. Acta, 365, pp. 279-287
Mirisola, M. G., Cal, F., Gloria, A., Schinocca, P., D'Amato, M., Cassar, G., Leo, G. D., Romano, V., PAH gene mutations in the Sicilian population: association with minihaplotypes and expression analysis (2001) Mol. Genet. Metab., 74, pp. 353-361
Muntau, A. C., Roschinger, W., Habich, M., Demmelmair, H. H., Hoffmann, B., Sommhoff, C. P., Roscher, A. A., Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria (2002) N. Engl. J. Med., 347, pp. 2122-2132
Pey, A. L., Perez, B., Desviat, L. R., Martinez, M. A., Aguado, C., Erlandsen, H., Gamez, A., Martinez, A., Mechanisms underlying responsiveness to tetrahydrobiopterin in mild phenylketonuria mutations (2004) Hum. Mutat., 24, pp. 388-399
Stokka, A. J., Carvalho, R. N., Barroso, J. F., Flatmark, T., Probing the role of crystallographically defined/predicted hinge-bending regions in the substrate-induced global conformational transition and catalytic activation of human phenylalanine hydroxylase by single-site mutagenesis (2004) J. Biol. Chem., 279, pp. 26571-26580
Bba-Gen Subjects (ISSN: 0925-4439, 0006-3002, 1570-9639), 2008 Jun; 1782(6): 378-384.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 2.233, 5-year impact factor: 2.816
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-43549124527&partnerID=40&md5=8844bbba125596993ff409c857bea650
Keywords: Expression Studies Of Pku Mutants, Pku Mutations, Pku Mutations Functional Analysis, Structural Analysis, Phenylalanine 4 Monooxygenase, Article, Controlled Study, Crystal Structure, Enzyme Activity, Gene Mutation, Human, Human Cell, Hyperphenylalaninemia, Italy, Loading Test, Pathogenesis, Phenotype, Priority Journal, Protein Analysis, Protein Expression, Reverse Transcription Polymerase Chain Reaction, Western Blotting, Cell Line, Dna Mutational Analysis, Genetic Predisposition To Disease, Models, Molecular, Phenylalanine Hydroxylase, Phenylketonurias, Protein Structure, Secondary, Reverse Transcriptase Polymerase Chain Reaction,
Affiliations:
*** IBB - CNR ***
CEINGE - Biotecnologie Avanzate Scarl, Via Comunale Margherita, 482, 80145 Naples, Italy
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Via S. Pansini, 5, 80131 Naples, Italy
Dipartimento di Scienze per la Salute, Università del Molise, Via F. De Sanctis, 86100 Campobasso, Italy
Centro Screening Fenilchetonuria, Ospedale SS. Annunziata, ASL Na1, Via Egiziaca a Forcella, 18, 80139 Naples, Italy
CNR - Istituto di Biostrutture e Bioimmagini, Via Mezzocannone, 16, 80134 Naples, Italy
SEMM - European School of Molecular Medicine, Naples Site - CEINGE, Italy
References:
C.R. Scriver, S. Kaufman, The hyperphenylalaninemias, in: C.R. Scriver, A.L. Beaudet, S.W. Sly, D. Valle (eds) B. Childs, K.W. Kinzler, B. Vogelstein (assoc. eds), The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 2001, 8 ed., Ch. 77Scriver, C.R., The PAH gene, phenylketonuria, and a paradigm shift (2007) Hum. Mutat., 28, pp. 831-84
Scriver, C.R., Waters, P.J., Monogenic traits are not simple. Lessons from phenylketonuria (1999) Trends Genet., 15, pp. 267-272
Kaufman, S., Hyperphenylalaninaemia caused by defects in biopterin metabolism (1985) J. Inherit. Metab. Dis., 8 (SUPPL. 1), pp. 20-27
Leuzzi, V., Carducci, C., Carducci, C., Chiarotti, F., Artiola, C., Giovanniello, T., Antonozzi, I., The spectrum of phenylalanine variations under tetrahydrobiopterin load in subjects affected by phenylalanine hydroxylase deficiency (2006) J. Inherit. Metab. Dis., 29, pp. 38-46
Hennermann, J.B., Bührer, C., Blau, N., Vetter, B., Mönch, E., Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria (2005) Mol. Genet. Metab., 86, pp. S86-S90
Fiori, L., Fiege, B., Riva, E., Giovannini, M., Incidence of BH4-responsiveness in phenylalanine-hydroxylase-deficient Italian patients (2005) Mol. Genet. Metab., 86, pp. S67-S74
Fiege, B., Bonafe, L., Ballhausen, D., Baumgartner, M., Thony, B., Meili, D., Fiori, L., Blau, N., Extended tetrahydrobiopterin loading test in the diagnosis of cofactor-responsive phenylketonuria: a pilot study (2005) Mol. Genet. Metab., 86, pp. S91-S95
Levy, H.L., Milanowski, A., Chakrapani, A., Cleary, M., Lee, P., Trefz, F.K., Whitley, C.B., Dorenbaum, A., Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study (2007) Lancet, 370, pp. 504-510
Burton, B.K., Grange, D.K., Milanowski, A., Vockley, G., Feillet, F., Crombez, E.A., Abadie, V., Dorenbaum, A., The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study (2007) Inherit. Metab. Dis., 30, pp. 700-707
Scriver, C.R., Hurtubise, M., Konecki, D., Phommarinh, M., Prevost, L., Erlandsen, H., Stevens, R., Sarkissian, C., PAHdb 2003: what a locus-specific knowledgebase can do? (2003) Hum. Mutat., 21, pp. 333-344
Blau, N., Erlandsen, H., The metabolic and molecular bases of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency (2004) Mol. Genet. Metab., 82, pp. 101-111
Perez, B., Desviat, L.R., Gomez-Puertas, P., Martinez, A., Stevens, R.C., Ugarte, M., Kinetic and stability analysis of PKU mutations identified in BH4-responsive patients (2005) Mol. Genet. Metab., 86 (SUPPL. 1), pp. S11-S16
Waters, P.J., How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression (2003) Hum. Mutat., 21, pp. 357-369
Daniele, A., Cardillo, G., Pennino, C., Carbone, M.T., Scognamiglio, D., Correra, A., Pignero, A., Salvatore, F., Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: a 96% detection rate with ten novel mutations (2007) Ann. Hum. Genet., 71, pp. 185-193
Erlandsen, H., Fusetti, F., Martinez, A., Hough, E., Flatmark, T., Stevens, R.C., Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria (1997) Nat. Struct. Biol., 4, pp. 995-1000
Andersen, O.A., Flatmark, T., Hough, E., Crystal structure of the ternary complex of the catalytic domain of human phenylalanine hydroxylase with tetrahydrobiopterin and 3-(2-thienyl)-l-alanine, and its implications for the mechanism of catalysis and substrate activation (2002) J. Mol. Biol., 320, pp. 1095-1108
Andersen, O.A., Stokka, A.J., Flatmark, T., Hough, E., 2.0Å resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3-(2-thienyl)-l-alanine or l-norleucine: substrate specificity and molecular motions related to substrate binding (2003) J. Mol. Biol., 333, pp. 747-757
Kim, S.W., Jung, J., Oh, H.J., Kim, J., Lee, K.S., Lee, D.H., Park, C., Jung, S.C., Structural and functional analyses of mutations of the human phenylalanine hydroxylase gene (2006) Clin. Chim. Acta, 365, pp. 279-287
Erlandsen, H., Patch, M.G., Gamez, A., Straub, M., Stevens, R.C., Structural studies on phenylalanine hydroxylase and implications toward understanding and treating phenylketonuria (2003) Pediatrics, 112, pp. 1557-1565
Erlandsen, H., Pey, A.L., Gamez, A., Perez, B., Desviat, L.R., Aguado, C., Koch, R., Stevens, R.C., Correction of kinetic and stability defects by tetrahydrobiopterin in phenylketonuria patients with certain phenylalanine hydroxylase mutations (2004) Proc. Natl. Acad. Sci. U. S. A., 101, pp. 16903-16908
Daniele, A., Di Natale, P., Heparan N-sulfatase: cysteine 70 plays a role in the enzyme catalysis and processing (2001) FEBS Lett., 505, pp. 445-448
Mirisola, M.G., Calì, F., Gloria, A., Schinocca, P., D'Amato, M., Cassarà, G., Leo, G.D., Romano, V., PAH gene mutations in the Sicilian population: association with minihaplotypes and expression analysis (2001) Mol. Genet. Metab., 74, pp. 353-361
Bardelli, T., Donati, M.A., Gasperini, S., Ciani, F., Belli, F., Blau, N., Morrone, A., Zammarchi, E., Two novel genetic lesions and a common BH4-responsive mutation of the PAH gene in Italian patients with hyperphenylalaninemia (2002) Mol. Genet. Metab., 77, pp. 260-266
Muntau, A.C., Roschinger, W., Habich, M., Demmelmair, H.H., Hoffmann, B., Sommhoff, C.P., Roscher, A.A., Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria (2002) N. Engl. J. Med., 347, pp. 2122-2132
Pey, A.L., Perez, B., Desviat, L.R., Martinez, M.A., Aguado, C., Erlandsen, H., Gamez, A., Martinez, A., Mechanisms underlying responsiveness to tetrahydrobiopterin in mild phenylketonuria mutations (2004) Hum. Mutat., 24, pp. 388-399
Kure, S., Sato, K., Fujii, K., Aoki, Y., Suzuki, Y., Kato, S., Matsubara, Y., Wild-type phenylalanine hydroxylase activity is enhanced by tetrahydrobiopterin supplementation in vivo: an implication for therapeutic basis of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency (2004) Mol. Genet. Metab., 83, pp. 150-156
Aguado, C., Perez, B., Ugarte, M., Desviat, L.R., Analysis of the effect of tetrahydrobiopterin on PAH gene expression in hepatoma cells (2006) FEBS Lett., 580, pp. 1697-1701
Giovannini, M., Verduci, E., Salvatici, E., Fiori, L., Riva, E., Phenylketonuria: dietary and therapeutic challenges (2007) J. Inherit. Metab. Dis., 30, pp. 145-152
Stokka, A.J., Carvalho, R.N., Barroso, J.F., Flatmark, T., Probing the role of crystallographically defined/predicted hinge-bending regions in the substrate-induced global conformational transition and catalytic activation of human phenylalanine hydroxylase by single-site mutagenesis (2004) J. Biol. Chem., 279, pp. 26571-26580
C. R. Scriver, S. Kaufman, The hyperphenylalaninemias, in: C. R. Scriver, A. L. Beaudet, S. W. Sly, D. Valle (eds) B. Childs, K. W. Kinzler, B. Vogelstein (assoc. eds), The Metabolic and Molecular Bases of Inherited Disease, McGraw-Hill, New York, 2001, 8 ed., Ch. 77Scriver, C. R., The PAH gene, phenylketonuria, and a paradigm shift (2007) Hum. Mutat., 28, pp. 831-84
Scriver, C. R., Waters, P. J., Monogenic traits are not simple. Lessons from phenylketonuria (1999) Trends Genet., 15, pp. 267-272
Hennermann, J. B., B hrer, C., Blau, N., Vetter, B., M nch, E., Long-term treatment with tetrahydrobiopterin increases phenylalanine tolerance in children with severe phenotype of phenylketonuria (2005) Mol. Genet. Metab., 86, pp. S86-S90
Levy, H. L., Milanowski, A., Chakrapani, A., Cleary, M., Lee, P., Trefz, F. K., Whitley, C. B., Dorenbaum, A., Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised placebo-controlled study (2007) Lancet, 370, pp. 504-510
Burton, B. K., Grange, D. K., Milanowski, A., Vockley, G., Feillet, F., Crombez, E. A., Abadie, V., Dorenbaum, A., The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study (2007) Inherit. Metab. Dis., 30, pp. 700-707
Scriver, C. R., Hurtubise, M., Konecki, D., Phommarinh, M., Prevost, L., Erlandsen, H., Stevens, R., Sarkissian, C., PAHdb 2003: what a locus-specific knowledgebase can do? (2003) Hum. Mutat., 21, pp. 333-344
Waters, P. J., How PAH gene mutations cause hyper-phenylalaninemia and why mechanism matters: insights from in vitro expression (2003) Hum. Mutat., 21, pp. 357-369
Andersen, O. A., Flatmark, T., Hough, E., Crystal structure of the ternary complex of the catalytic domain of human phenylalanine hydroxylase with tetrahydrobiopterin and 3- (2-thienyl) -l-alanine, and its implications for the mechanism of catalysis and substrate activation (2002) J. Mol. Biol., 320, pp. 1095-1108
Andersen, O. A., Stokka, A. J., Flatmark, T., Hough, E., 2. 0 resolution crystal structures of the ternary complexes of human phenylalanine hydroxylase catalytic domain with tetrahydrobiopterin and 3- (2-thienyl) -l-alanine or l-norleucine: substrate specificity and molecular motions related to substrate binding (2003) J. Mol. Biol., 333, pp. 747-757
Kim, S. W., Jung, J., Oh, H. J., Kim, J., Lee, K. S., Lee, D. H., Park, C., Jung, S. C., Structural and functional analyses of mutations of the human phenylalanine hydroxylase gene (2006) Clin. Chim. Acta, 365, pp. 279-287
Mirisola, M. G., Cal, F., Gloria, A., Schinocca, P., D'Amato, M., Cassar, G., Leo, G. D., Romano, V., PAH gene mutations in the Sicilian population: association with minihaplotypes and expression analysis (2001) Mol. Genet. Metab., 74, pp. 353-361
Muntau, A. C., Roschinger, W., Habich, M., Demmelmair, H. H., Hoffmann, B., Sommhoff, C. P., Roscher, A. A., Tetrahydrobiopterin as an alternative treatment for mild phenylketonuria (2002) N. Engl. J. Med., 347, pp. 2122-2132
Pey, A. L., Perez, B., Desviat, L. R., Martinez, M. A., Aguado, C., Erlandsen, H., Gamez, A., Martinez, A., Mechanisms underlying responsiveness to tetrahydrobiopterin in mild phenylketonuria mutations (2004) Hum. Mutat., 24, pp. 388-399
Stokka, A. J., Carvalho, R. N., Barroso, J. F., Flatmark, T., Probing the role of crystallographically defined/predicted hinge-bending regions in the substrate-induced global conformational transition and catalytic activation of human phenylalanine hydroxylase by single-site mutagenesis (2004) J. Biol. Chem., 279, pp. 26571-26580
Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants
Hyperphenylalaninemia is a group of autosomal recessive disorders caused by a wide range of phenylalanine hydroxylase (PAH) gene variants. To study the effects of mutations on PAH activity, we have reproduced five mutations (p.N223Y, p.R297L, p.F382L, p.K398N and p.Q419R) that we recently identified in a population of Southern Italy. Transient expression of mutant full-length cDNAs in human HEK293 cells yielded PAH variants whose L-phenylalanine hydroxylase activity was between 40% and 70% that of the wild-type enzyme. Moreover, Western blot analysis revealed a 50-kD monomer in all mutants thereby indicating normal synthesis of the mutant proteins. Because of the clinical mild nature of the phenotypes we performed an in vivo BH4 loading test. This was positive in all tested patients, which indicates that they are likely to respond to the coenzyme in vivo. We also analysed the environment of each mutation site in the available crystal structures of PAH by using molecular graphics tools. The structural alteration produced by each mutation was elucidated and correlated to the mutated properties of the mutant enzymes. All the data obtained demonstrate the disease-causing nature of the five novel variants. (C) 2008 Elsevier B.V. All rights reserved.
Hyperphenylalaninemia is a group of autosomal recessive disorders caused by a wide range of phenylalanine hydroxylase (PAH) gene variants. To study the effects of mutations on PAH activity, we have reproduced five mutations (p.N223Y, p.R297L, p.F382L, p.K398N and p.Q419R) that we recently identified in a population of Southern Italy. Transient expression of mutant full-length cDNAs in human HEK293 cells yielded PAH variants whose L-phenylalanine hydroxylase activity was between 40% and 70% that of the wild-type enzyme. Moreover, Western blot analysis revealed a 50-kD monomer in all mutants thereby indicating normal synthesis of the mutant proteins. Because of the clinical mild nature of the phenotypes we performed an in vivo BH4 loading test. This was positive in all tested patients, which indicates that they are likely to respond to the coenzyme in vivo. We also analysed the environment of each mutation site in the available crystal structures of PAH by using molecular graphics tools. The structural alteration produced by each mutation was elucidated and correlated to the mutated properties of the mutant enzymes. All the data obtained demonstrate the disease-causing nature of the five novel variants. (C) 2008 Elsevier B.V. All rights reserved.
Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants
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Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants
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Monti A, Sturlese M, Caporale A, Roger JA, Mascanzoni F, Ruvo M, Doti N
* Design, synthesis, structural analysis and biochemical studies of stapled AIF(370-394) analogues as ligand of CypA (87 views)
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Gautier B, Goncalves V, Diana D, Di Stasi R, Teillet F, Lenoir C, Huguenot F, Garbay C, Fattorusso R, D'Andrea LD, Vidal M, Inguimbert N
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Diana D, Ziaco B, Scarabelli G, Pedone C, Colombo G, D'Andrea LD, Fattorusso R
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Chemistry (ISSN: 1521-3765, 0947-6539, 1521-3765electronic), 2010 May 10; 16(18): 5400-5407.
Impact Factor: 5.476
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D'Ambrosio K, Limauro D, Pedone E, Galdi I, Pedone C, Bartolucci S, De Simone G
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Di Fiore A, Fiorentino G, Vitale RM, Ronca R, Amodeo P, Pedone C, Bartolucci S, De Simone G
* Structural analysis of BldR from Sulfolobus solfataricus provides insights into the molecular basis of transcriptional activation in Archaea by MarR family proteins (470 views)
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Impact Factor: 3.871
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Daniele A, Scala I, Cardillo G, Pennino C, Ungaro C, Sibilio M, Parenti G, Esposito L, Zagari A, Andria G, Salvatore F
* Functional and structural characterization of novel mutations and genotype-phenotype correlation in 51 phenylalanine hydroxylase deficient families from Southern Italy (423 views)
Febs Journal (ISSN: 1742-464x), 2009 Apr; 276(7): 2048-2059.
Impact Factor: 3.042
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Santelli E, Leone M, Li C, Fukushima T, Preece NE, Olson AJ, Ely KR, Reed JC, Pellecchia M, Liddington RC, Matsuzawa S-I
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De Simone G, Mandrich L, Menchise V, Giordano V, Febbraio F, Rossi M, Pedone C, Manco G
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Saviano M, Isernia C, Rossi F, Di Blasio B, Iacovino R, Mazzeo M, Pedone C, Benedetti E
Solid state structural analysis of the cyclooctapeptide cyclo-(Pro(1)-Pro-Phe-Phe-Ac(6)c-Ile-D-Ala-Val(8)) (426 views)
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Pavone V, De Simone G, Nastri F, Galdiero S, Staiano N, Lombardi A, Pedone C
Multiple binding mode of reversible synthetic thrombin inhibitors. A comparative structural analysis (589 views)
Biol Chem Biological Chemistry (ISSN: 1431-6730, 1437-4315), 1998 Sep; 379(8-9): 987-1006.
Impact Factor: 2.636
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Lombardi A, Maglio O, Benedetti B, Di Blasio E, Saviano M, Nastri F, Pedone C, Pavone V
Pt(II) Complexes of Amino Acids and Peptides. II. Structural Analysis of trans-[Cl2-Pt-(H-Aib-OH)2] (429 views)
Inorg Chim Acta, 1992; 196: 241-246.
Impact Factor: 0
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* Design, synthesis, structural analysis and biochemical studies of stapled AIF(370-394) analogues as ligand of CypA (87 views)
Bba-Gen Subjects (ISSN: 0304-4165linking, 0005-2728, 0006-3002print), 2020 Dec; 1864(12): 129717-129717.
Impact Factor: 3.422
View Export to BibTeX Export to EndNote
Mercurio FA, Pirone L, Di Natale C, Marasco D, Pedone EM, Leone M
* Sam domain-based stapled peptides: Structural analysis and interaction studies with the Sam domains from the EphA2 receptor and the lipid phosphatase Ship2 (327 views)
Bioorg Chem (ISSN: 0045-2068linking, 1090-2120electronic), 2018 Oct; 80: 602-610.
Impact Factor: 3.9
View Export to BibTeX Export to EndNote
Speciale I, Paciello I, Fazio LL, Sturiale L, Palmigiano A, Lanzetta R, Parrilli M, Garozzo D, Lemaitre B, Bernardini ML, Molinaro A, De Castro C
* Determination of the structure of the O-antigen and the lipid A from the entomopathogenic bacterium Pseudomonas entomophila lipopolysaccharide along with its immunological properties (387 views)
Carbohyd Res (ISSN: 0008-6215, 0008-6215linking), 2015; 412: 20-27.
Impact Factor: 1.817
View Export to BibTeX Export to EndNote
Di Lorenzo F, Silipo A, Bianconi I, Lore' NI, Scamporrino A, Sturiale L, Garozzo D, Lanzetta R, Parrilli M, Bragonzi A, Molinaro A
* Persistent cystic fibrosis isolate Pseudomonas aeruginosa strain RP73 exhibits an under-acylated LPS structure responsible of its low inflammatory activity (363 views)
Mol Immunol (ISSN: 0161-5890), 2015; 63(2): 166-175.
Impact Factor: 3.375
View Export to BibTeX Export to EndNote
Gautier B, Goncalves V, Diana D, Di Stasi R, Teillet F, Lenoir C, Huguenot F, Garbay C, Fattorusso R, D'Andrea LD, Vidal M, Inguimbert N
* Biochemical and Structural Analysis of the Binding Determinants of a Vascular Endothelial Growth Factor Receptor Peptidic Antagonist (496 views)
J Med Chem (ISSN: 0022-2623, 1520-4804, 0022-2623print), 2010 Jun 10; 53(11): 4428-4440.
Impact Factor: 5.207
View Export to BibTeX Export to EndNote
Diana D, Ziaco B, Scarabelli G, Pedone C, Colombo G, D'Andrea LD, Fattorusso R
* Structural analysis of a helical peptide unfolding pathway (461 views)
Chemistry (ISSN: 1521-3765, 0947-6539, 1521-3765electronic), 2010 May 10; 16(18): 5400-5407.
Impact Factor: 5.476
View Export to BibTeX Export to EndNote
D'Ambrosio K, Limauro D, Pedone E, Galdi I, Pedone C, Bartolucci S, De Simone G
* Insights into the catalytic mechanism of the Bcp family: functional and structural analysis of Bcp1 from Sulfolobus solfataricus (469 views)
Proteins (ISSN: 1097-0134, 0887-3585, 1097-0134electronic), 2009 Sep; 76(4): 995-1006.
Impact Factor: 3.085
View Export to BibTeX Export to EndNote
Di Fiore A, Fiorentino G, Vitale RM, Ronca R, Amodeo P, Pedone C, Bartolucci S, De Simone G
* Structural analysis of BldR from Sulfolobus solfataricus provides insights into the molecular basis of transcriptional activation in Archaea by MarR family proteins (470 views)
J Mol Biol (ISSN: 1089-8638, 0022-2836, 1089-8638electronic), 2009 May 8; 388(3): 559-569.
Impact Factor: 3.871
View Export to BibTeX Export to EndNote
Daniele A, Scala I, Cardillo G, Pennino C, Ungaro C, Sibilio M, Parenti G, Esposito L, Zagari A, Andria G, Salvatore F
* Functional and structural characterization of novel mutations and genotype-phenotype correlation in 51 phenylalanine hydroxylase deficient families from Southern Italy (423 views)
Febs Journal (ISSN: 1742-464x), 2009 Apr; 276(7): 2048-2059.
Impact Factor: 3.042
View Export to BibTeX Export to EndNote
Santelli E, Leone M, Li C, Fukushima T, Preece NE, Olson AJ, Ely KR, Reed JC, Pellecchia M, Liddington RC, Matsuzawa S-I
* Structural analysis of Siah1-Siah-interacting protein interactions and insights into the assembly of an E3 ligase multiprotein complex (406 views)
Jbc Papers (ISSN: 0021-9258, 1083-351x, 0021-9258linking), 2005 Oct 7; 280(40): 34278-34287.
Impact Factor: 5.854
View Export to BibTeX Export to EndNote
De Simone G, Mandrich L, Menchise V, Giordano V, Febbraio F, Rossi M, Pedone C, Manco G
* A substrate-induced switch in the reaction mechanism of a thermophilic esterase - Kinetic evidences and structural basis (409 views)
Jbc Papers (ISSN: 0021-9258, 1083-351x, 0021-9258linking), 2004 Feb 20; 279(8): 6815-6823.
Impact Factor: 6.355
View Export to BibTeX Export to EndNote
Saviano M, Isernia C, Rossi F, Di Blasio B, Iacovino R, Mazzeo M, Pedone C, Benedetti E
Solid state structural analysis of the cyclooctapeptide cyclo-(Pro(1)-Pro-Phe-Phe-Ac(6)c-Ile-D-Ala-Val(8)) (426 views)
Biopolymers (ISSN: 0006-3525, 0006-6352, 0006-3525print), 2000 Feb; 53(2): 189-199.
Impact Factor: 2.405
View Export to BibTeX Export to EndNote
Pavone V, De Simone G, Nastri F, Galdiero S, Staiano N, Lombardi A, Pedone C
Multiple binding mode of reversible synthetic thrombin inhibitors. A comparative structural analysis (589 views)
Biol Chem Biological Chemistry (ISSN: 1431-6730, 1437-4315), 1998 Sep; 379(8-9): 987-1006.
Impact Factor: 2.636
View Export to BibTeX Export to EndNote
Lombardi A, Maglio O, Benedetti B, Di Blasio E, Saviano M, Nastri F, Pedone C, Pavone V
Pt(II) Complexes of Amino Acids and Peptides. II. Structural Analysis of trans-[Cl2-Pt-(H-Aib-OH)2] (429 views)
Inorg Chim Acta, 1992; 196: 241-246.
Impact Factor: 0
View Export to BibTeX Export to EndNote
14 Records (14 excluding Abstracts).
Total impact factor: 50.445 (50.445 excluding Abstracts).
Total 5 year impact factor: 49.949 (49.949 excluding Abstracts).
Total impact factor: 50.445 (50.445 excluding Abstracts).
Total 5 year impact factor: 49.949 (49.949 excluding Abstracts).
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