Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function (378 views)
Biochem J (ISSN: 0264-6021, 1470-8728electronic, 0264-6021linking), 2004 May 15; 380: 51-56.
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Paper type: Journal Article,
Impact factor: 4.278, 5-year impact factor: 4.95
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-2642534395&partnerID=40&md5=9a67fef59be66b14431663cb5d63cbe7
Keywords: Aldolase A, Aldolase A Gene Mutation, Aldolase A Mutant Expression, Fructose 1, 6-Bisphosphate, Molecular Modelling, Bacteria, Conformations, Enzymes, Molecular Graphics, Anemia, Myopathic Symptoms, Biochemistry, Complementary Dna, 6 Bisphosphate, Fructose Bisphosphate Aldolase, Hydrolase, Mutant Protein, Arthrogryposis, Article, Birth, Carboxy Terminal Sequence, Controlled Study, Crystallography, Ectopic Tissue, Enzyme Activity, Enzyme Deficiency, Hemolytic Anemia, Heterozygosity, Human, Melting Point, Priority Journal, Protein Analysis, Protein Expression, Protein Function, School Child, Sequence Analysis, Substitution Reaction, Temperature Measurement, Wild Type, Amino Acid Substitution, Congenital, Circular Dichroism, Codon, Fructose-Bisphosphate Aldolase, Glycine, Infant, Kinetics, Molecular Weight, Muscle Weakness, Mutagenesis, Site-Directed, Missense, Point Mutation, Protein Conformation, Protein Denaturation, Protein Structure, Tertiary, Recombinant Fusion Proteins, Structure-Activity Relationship, Bacteria (microorganisms), Felis Catus, Oryctolagus Cuniculus,
Affiliations:
*** IBB - CNR ***
Dipto. Biochim. Biotecnologie M., Univ. di Napoli Federico II, Via S. Pansini 5, I-80131 Napoli, Italy
CEINGE-Biotecnologie Avanzate, Univ. di Napoli Federico II, Via S. Pansini 5, I-80131 Napoli, Italy
Ist. di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 6, I-80134 Napoli, Italy
Dipartimento di Pediatria, Policlinico, Università di Catania, Via S. Sofia 78, I-95123 Catania, Italy
Dipartimento di Chimica Biologica, Univ. di Napoli Federico II, Via Mezzocannone 6, I-80134 Napoli, Italy
References:
Salvatore, F., Izzo, P., Paolella, G., Aldolase gene and protein families: Structure, expression and pathophysiology (1986) Horizons in Biochemistry Biophysics, 8, pp. 611-665. , Blasi, F., ed., John Wiley and Sons, Chicheste
Steinmann, B., Gitzelmann, R., Van Den Berghe, G., Disorders of fructose metabolism (2001) The Metabolic and Molecular Bases of Inherited Disease, 7th Edn, pp. 1489-1520. , Scriver, C. S., Beaudet, A. L., Sly, W. S. and Valle, D., eds., McGraw-Hill, New York
Ali, M., Rellos, P., Cox, T., Hereditary fructose intolerance (1998) J. Med. Genet., 35, pp. 353-365
Santamaria, R., Scarano, M.I., Esposito, G., Chiandetti, L., Izzo, P., Salvatore, F., The molecular basis of hereditary fructose intolerance in Italian children (1993) Eur. J. Clin. Chem. Clin. Biochem., 31, pp. 675-678
Santamaria, R., Tamasi, S., Del Piano, G., Sebastio, G., Andria, G., Borrone, C., Faldella, G., Salvatore, F., Molecular basis of hereditary fructose intolerance in Italy: Identification of two novel mutations in the aldolase B gene (1996) J. Med. Genet., 33, pp. 786-788
Santamaria, R., Vitagliano, L., Tamasi, S., Izzo, P., Zancan, L., Zagari, A., Salvatore, F., Novel six-nucleotide deletion in the hepatic fructose-1,6-bisphosphate aldolase gene in a patient with hereditary fructose intolerance and enzyme structure-function implications (1999) Eur. J. Hum. Genet., 7, pp. 409-414
Santamaria, R., Esposito, G., Vitagliano, L., Race, V., Paglionico, I., Zancan, L., Zagari, A., Salvatore, F., Functional and molecular modelling studies of two hereditary fructose intolerance-causing mutations at arginine 303 in human liver aldolase (2000) Biochem. J., 350, pp. 823-828
Beutler, E., Scott, S., Bishop, A., Margolis, N., Matsumoto, F., Kuhl, W., Red cell aldolase deficiency and hemolytic anemia: A new syndrome (1973) Trans. Assoc. Am. Phys., 86, pp. 154-166
Miwa, S., Fujii, H., Tani, K., Takahashi, K., Takegawa, S., Fujinami, N., Sakurai, M., Matsumoto, N., Two cases of red cell aldolase deficiency associated with hereditary hemolytic anemia in a Japanese family (1981) Am. J. Hemat., 11, pp. 425-437
Kishi, H., Mukai, T., Hirono, A., Fujii, H., Miwa, S., Hori, K., Human aldolase A deficiency associated with a hemolytic anemia: Thermolabile aldolase due to a single base mutation (1987) Proc. Nat. Acad. Sci. U.S.A., 84, pp. 8623-8627
Kreuder, J., Borkhardt, A., Repp, R., Pekrun, A., Gottsche, B., Gottschalk, U., Reichmann, H., Lampert, F., Brief report: Inherited metabolic myopathy and hemolysis due to a mutation in aldolase A (1996) New Eng. J. Med., 334, pp. 1100-1104
Hurst, J.A., Baraitser, M., Winter, R.M., A syndrome of mental retardation, short stature, hemolytic anemia, delayed puberty, and abnormal facial appearance: Similarities to a report of aldolase A deficiency (1987) Am. J. Med. Genet., 28, pp. 965-970
Parano, E., Trifiletti, R.R., Barone, R., Pavone, P., Pavone, V., Arthrogryposis multiplex congenita and pituitary ectopia: A case report (2000) Neuropediatrics, 31, pp. 325-327
Miller, S.A., Dykes, D.D., Polesky, H.F., A simple salting out procedure for extracting DNA from human nucleated cells (1988) Nucleic Acids Res., 16, p. 1215
Newton, C.R., Graham, A., Heptinstall, L.E., Powell, S.J., Summers, C., Kalsheker, N., Smith, J.C., Markham, A.F., Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS) (1989) Nucleic Acids Res., 17, pp. 2503-2516
Izzo, P., Costanzo, P., Lupo, A., Rippa, E., Paolella, G., Salvatore, F., Human aldolase A gene: Structural organization and tissue-specific expression by multiple promoters and alternate mRNA processing (1988) Eur. J. Biochem., 174, pp. 569-578
Morris, A.J., Tolan, D.R., Site-directed mutagenesis identifies aspartate 33 as a previously unidentified critical residue in the catalytic mechanism of rabbit aldolase A (1993) J. Biol. Chem., 268, pp. 1095-1110
Berman, H.M., Bhat, T.N., Bourne, P.E., Feng, Z., Gilliland, G., Weissig, H., Westbrook, J., The Protein Data Bank and the challenge of structural genomics (2000) Nat. Struct. Biol., 7, pp. 957-959
Gamblin, S.J., Davies, G.J., Grimes, J.M., Jackson, R.M., Littlechild, J.A., Watson, H.C., Activity and specificity of human aldolases (1991) J. Mol. Biol., 219, pp. 573-576
Blom, N., Sygusch, J., Product binding and role of the C-terminal region in class I D-fructose 1,6-bisphosphate aldolase (1997) Nat. Struct. Biol., 4, pp. 36-39
Dalby, A., Dauter, Z., Littlechild, J.A., Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate: Mechanistic implications (1999) Protein Sci., 8, pp. 291-297
Choi, K.H., Mazurkie, A.S., Morris, A.J., Utheza, D., Tolan, D.R., Allen, K.N., Structure of a fructose-1,6-bis(phosphate) aldolase liganded to its natural substrate in a cleavage-defective mutant at 2.3 Å (1999) Biochemistry, 38, pp. 12655-12664
Choi, K.H., Shi, J., Hopkins, C.E., Tolan, D.R., Allen, K.N., Snapshots of catalysis: The structure of fructose-1,6-(bis)phosphate aldolase covalently bound to the substrate dihydroxyacetone phosphate (2001) Biochemistry, 40, pp. 13868-13875
Maurady, A., Zdanov, A., De Moissac, D., Beaudry, D., Sygusch, J., A conserved glutamate residue exhibits multifunctional catalytic roles in D-fructose-1,6-bisphosphate aldolases (2002) J. Biol. Chem., 277, pp. 9474-9483
Hutchinson, E.G., Thornton, J.M., PROMOTIF - A program to identify and analyse structural motifs in proteins (1996) Protein Sci., 5, pp. 212-220
Jones, T.A., Kjeldgaard, M., Electron-density map interpretation (1997) Methods Enzymol., 277, pp. 173-208
Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M., PROCHECK: A program to check the stereochemical quality of protein structures (1993) J. Appl. Crystallogr., 26, pp. 283-291
Kraulis, P.J., MolScript: A program to produce both detailed and schematic plots of protein structures (1991) J. Appl. Crystallogr., 24, pp. 945-949
Merritt, E.A., Bacon, D.J., Raster3D: Photorealistic molecular graphics (1997) Methods Enzymol., 277, pp. 505-524
Minakami, S.Y., Oshikawa, H., Thermodynamic considerations on erythrocyte glycolysis (1965) Biochem. Biophys. Res. Commun., 18, pp. 345-349
Hurst, J. A., Baraitser, M., Winter, R. M., A syndrome of mental retardation, short stature, hemolytic anemia, delayed puberty, and abnormal facial appearance: Similarities to a report of aldolase A deficiency (1987) Am. J. Med. Genet., 28, pp. 965-970
Miller, S. A., Dykes, D. D., Polesky, H. F., A simple salting out procedure for extracting DNA from human nucleated cells (1988) Nucleic Acids Res., 16, p. 1215
Newton, C. R., Graham, A., Heptinstall, L. E., Powell, S. J., Summers, C., Kalsheker, N., Smith, J. C., Markham, A. F., Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS) (1989) Nucleic Acids Res., 17, pp. 2503-2516
Morris, A. J., Tolan, D. R., Site-directed mutagenesis identifies aspartate 33 as a previously unidentified critical residue in the catalytic mechanism of rabbit aldolase A (1993) J. Biol. Chem., 268, pp. 1095-1110
Berman, H. M., Bhat, T. N., Bourne, P. E., Feng, Z., Gilliland, G., Weissig, H., Westbrook, J., The Protein Data Bank and the challenge of structural genomics (2000) Nat. Struct. Biol., 7, pp. 957-959
Gamblin, S. J., Davies, G. J., Grimes, J. M., Jackson, R. M., Littlechild, J. A., Watson, H. C., Activity and specificity of human aldolases (1991) J. Mol. Biol., 219, pp. 573-576
Choi, K. H., Mazurkie, A. S., Morris, A. J., Utheza, D., Tolan, D. R., Allen, K. N., Structure of a fructose-1, 6-bis (phosphate) aldolase liganded to its natural substrate in a cleavage-defective mutant at 2. 3 (1999) Biochemistry, 38, pp. 12655-12664
Choi, K. H., Shi, J., Hopkins, C. E., Tolan, D. R., Allen, K. N., Snapshots of catalysis: The structure of fructose-1, 6- (bis) phosphate aldolase covalently bound to the substrate dihydroxyacetone phosphate (2001) Biochemistry, 40, pp. 13868-13875
Hutchinson, E. G., Thornton, J. M., PROMOTIF - A program to identify and analyse structural motifs in proteins (1996) Protein Sci., 5, pp. 212-220
Jones, T. A., Kjeldgaard, M., Electron-density map interpretation (1997) Methods Enzymol., 277, pp. 173-208
Laskowski, R. A., MacArthur, M. W., Moss, D. S., Thornton, J. M., PROCHECK: A program to check the stereochemical quality of protein structures (1993) J. Appl. Crystallogr., 26, pp. 283-291
Kraulis, P. J., MolScript: A program to produce both detailed and schematic plots of protein structures (1991) J. Appl. Crystallogr., 24, pp. 945-949
Merritt, E. A., Bacon, D. J., Raster3D: Photorealistic molecular graphics (1997) Methods Enzymol., 277, pp. 505-524
Minakami, S. Y., Oshikawa, H., Thermodynamic considerations on erythrocyte glycolysis (1965) Biochem. Biophys. Res. Commun., 18, pp. 345-349
Biochem J (ISSN: 0264-6021, 1470-8728electronic, 0264-6021linking), 2004 May 15; 380: 51-56.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 4.278, 5-year impact factor: 4.95
Url: http://www.scopus.com/inward/record.url?eid=2-s2.0-2642534395&partnerID=40&md5=9a67fef59be66b14431663cb5d63cbe7
Keywords: Aldolase A, Aldolase A Gene Mutation, Aldolase A Mutant Expression, Fructose 1, 6-Bisphosphate, Molecular Modelling, Bacteria, Conformations, Enzymes, Molecular Graphics, Anemia, Myopathic Symptoms, Biochemistry, Complementary Dna, 6 Bisphosphate, Fructose Bisphosphate Aldolase, Hydrolase, Mutant Protein, Arthrogryposis, Article, Birth, Carboxy Terminal Sequence, Controlled Study, Crystallography, Ectopic Tissue, Enzyme Activity, Enzyme Deficiency, Hemolytic Anemia, Heterozygosity, Human, Melting Point, Priority Journal, Protein Analysis, Protein Expression, Protein Function, School Child, Sequence Analysis, Substitution Reaction, Temperature Measurement, Wild Type, Amino Acid Substitution, Congenital, Circular Dichroism, Codon, Fructose-Bisphosphate Aldolase, Glycine, Infant, Kinetics, Molecular Weight, Muscle Weakness, Mutagenesis, Site-Directed, Missense, Point Mutation, Protein Conformation, Protein Denaturation, Protein Structure, Tertiary, Recombinant Fusion Proteins, Structure-Activity Relationship, Bacteria (microorganisms), Felis Catus, Oryctolagus Cuniculus,
Affiliations:
*** IBB - CNR ***
Dipto. Biochim. Biotecnologie M., Univ. di Napoli Federico II, Via S. Pansini 5, I-80131 Napoli, Italy
CEINGE-Biotecnologie Avanzate, Univ. di Napoli Federico II, Via S. Pansini 5, I-80131 Napoli, Italy
Ist. di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 6, I-80134 Napoli, Italy
Dipartimento di Pediatria, Policlinico, Università di Catania, Via S. Sofia 78, I-95123 Catania, Italy
Dipartimento di Chimica Biologica, Univ. di Napoli Federico II, Via Mezzocannone 6, I-80134 Napoli, Italy
References:
Salvatore, F., Izzo, P., Paolella, G., Aldolase gene and protein families: Structure, expression and pathophysiology (1986) Horizons in Biochemistry Biophysics, 8, pp. 611-665. , Blasi, F., ed., John Wiley and Sons, Chicheste
Steinmann, B., Gitzelmann, R., Van Den Berghe, G., Disorders of fructose metabolism (2001) The Metabolic and Molecular Bases of Inherited Disease, 7th Edn, pp. 1489-1520. , Scriver, C. S., Beaudet, A. L., Sly, W. S. and Valle, D., eds., McGraw-Hill, New York
Ali, M., Rellos, P., Cox, T., Hereditary fructose intolerance (1998) J. Med. Genet., 35, pp. 353-365
Santamaria, R., Scarano, M.I., Esposito, G., Chiandetti, L., Izzo, P., Salvatore, F., The molecular basis of hereditary fructose intolerance in Italian children (1993) Eur. J. Clin. Chem. Clin. Biochem., 31, pp. 675-678
Santamaria, R., Tamasi, S., Del Piano, G., Sebastio, G., Andria, G., Borrone, C., Faldella, G., Salvatore, F., Molecular basis of hereditary fructose intolerance in Italy: Identification of two novel mutations in the aldolase B gene (1996) J. Med. Genet., 33, pp. 786-788
Santamaria, R., Vitagliano, L., Tamasi, S., Izzo, P., Zancan, L., Zagari, A., Salvatore, F., Novel six-nucleotide deletion in the hepatic fructose-1,6-bisphosphate aldolase gene in a patient with hereditary fructose intolerance and enzyme structure-function implications (1999) Eur. J. Hum. Genet., 7, pp. 409-414
Santamaria, R., Esposito, G., Vitagliano, L., Race, V., Paglionico, I., Zancan, L., Zagari, A., Salvatore, F., Functional and molecular modelling studies of two hereditary fructose intolerance-causing mutations at arginine 303 in human liver aldolase (2000) Biochem. J., 350, pp. 823-828
Beutler, E., Scott, S., Bishop, A., Margolis, N., Matsumoto, F., Kuhl, W., Red cell aldolase deficiency and hemolytic anemia: A new syndrome (1973) Trans. Assoc. Am. Phys., 86, pp. 154-166
Miwa, S., Fujii, H., Tani, K., Takahashi, K., Takegawa, S., Fujinami, N., Sakurai, M., Matsumoto, N., Two cases of red cell aldolase deficiency associated with hereditary hemolytic anemia in a Japanese family (1981) Am. J. Hemat., 11, pp. 425-437
Kishi, H., Mukai, T., Hirono, A., Fujii, H., Miwa, S., Hori, K., Human aldolase A deficiency associated with a hemolytic anemia: Thermolabile aldolase due to a single base mutation (1987) Proc. Nat. Acad. Sci. U.S.A., 84, pp. 8623-8627
Kreuder, J., Borkhardt, A., Repp, R., Pekrun, A., Gottsche, B., Gottschalk, U., Reichmann, H., Lampert, F., Brief report: Inherited metabolic myopathy and hemolysis due to a mutation in aldolase A (1996) New Eng. J. Med., 334, pp. 1100-1104
Hurst, J.A., Baraitser, M., Winter, R.M., A syndrome of mental retardation, short stature, hemolytic anemia, delayed puberty, and abnormal facial appearance: Similarities to a report of aldolase A deficiency (1987) Am. J. Med. Genet., 28, pp. 965-970
Parano, E., Trifiletti, R.R., Barone, R., Pavone, P., Pavone, V., Arthrogryposis multiplex congenita and pituitary ectopia: A case report (2000) Neuropediatrics, 31, pp. 325-327
Miller, S.A., Dykes, D.D., Polesky, H.F., A simple salting out procedure for extracting DNA from human nucleated cells (1988) Nucleic Acids Res., 16, p. 1215
Newton, C.R., Graham, A., Heptinstall, L.E., Powell, S.J., Summers, C., Kalsheker, N., Smith, J.C., Markham, A.F., Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS) (1989) Nucleic Acids Res., 17, pp. 2503-2516
Izzo, P., Costanzo, P., Lupo, A., Rippa, E., Paolella, G., Salvatore, F., Human aldolase A gene: Structural organization and tissue-specific expression by multiple promoters and alternate mRNA processing (1988) Eur. J. Biochem., 174, pp. 569-578
Morris, A.J., Tolan, D.R., Site-directed mutagenesis identifies aspartate 33 as a previously unidentified critical residue in the catalytic mechanism of rabbit aldolase A (1993) J. Biol. Chem., 268, pp. 1095-1110
Berman, H.M., Bhat, T.N., Bourne, P.E., Feng, Z., Gilliland, G., Weissig, H., Westbrook, J., The Protein Data Bank and the challenge of structural genomics (2000) Nat. Struct. Biol., 7, pp. 957-959
Gamblin, S.J., Davies, G.J., Grimes, J.M., Jackson, R.M., Littlechild, J.A., Watson, H.C., Activity and specificity of human aldolases (1991) J. Mol. Biol., 219, pp. 573-576
Blom, N., Sygusch, J., Product binding and role of the C-terminal region in class I D-fructose 1,6-bisphosphate aldolase (1997) Nat. Struct. Biol., 4, pp. 36-39
Dalby, A., Dauter, Z., Littlechild, J.A., Crystal structure of human muscle aldolase complexed with fructose 1,6-bisphosphate: Mechanistic implications (1999) Protein Sci., 8, pp. 291-297
Choi, K.H., Mazurkie, A.S., Morris, A.J., Utheza, D., Tolan, D.R., Allen, K.N., Structure of a fructose-1,6-bis(phosphate) aldolase liganded to its natural substrate in a cleavage-defective mutant at 2.3 Å (1999) Biochemistry, 38, pp. 12655-12664
Choi, K.H., Shi, J., Hopkins, C.E., Tolan, D.R., Allen, K.N., Snapshots of catalysis: The structure of fructose-1,6-(bis)phosphate aldolase covalently bound to the substrate dihydroxyacetone phosphate (2001) Biochemistry, 40, pp. 13868-13875
Maurady, A., Zdanov, A., De Moissac, D., Beaudry, D., Sygusch, J., A conserved glutamate residue exhibits multifunctional catalytic roles in D-fructose-1,6-bisphosphate aldolases (2002) J. Biol. Chem., 277, pp. 9474-9483
Hutchinson, E.G., Thornton, J.M., PROMOTIF - A program to identify and analyse structural motifs in proteins (1996) Protein Sci., 5, pp. 212-220
Jones, T.A., Kjeldgaard, M., Electron-density map interpretation (1997) Methods Enzymol., 277, pp. 173-208
Laskowski, R.A., MacArthur, M.W., Moss, D.S., Thornton, J.M., PROCHECK: A program to check the stereochemical quality of protein structures (1993) J. Appl. Crystallogr., 26, pp. 283-291
Kraulis, P.J., MolScript: A program to produce both detailed and schematic plots of protein structures (1991) J. Appl. Crystallogr., 24, pp. 945-949
Merritt, E.A., Bacon, D.J., Raster3D: Photorealistic molecular graphics (1997) Methods Enzymol., 277, pp. 505-524
Minakami, S.Y., Oshikawa, H., Thermodynamic considerations on erythrocyte glycolysis (1965) Biochem. Biophys. Res. Commun., 18, pp. 345-349
Hurst, J. A., Baraitser, M., Winter, R. M., A syndrome of mental retardation, short stature, hemolytic anemia, delayed puberty, and abnormal facial appearance: Similarities to a report of aldolase A deficiency (1987) Am. J. Med. Genet., 28, pp. 965-970
Miller, S. A., Dykes, D. D., Polesky, H. F., A simple salting out procedure for extracting DNA from human nucleated cells (1988) Nucleic Acids Res., 16, p. 1215
Newton, C. R., Graham, A., Heptinstall, L. E., Powell, S. J., Summers, C., Kalsheker, N., Smith, J. C., Markham, A. F., Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS) (1989) Nucleic Acids Res., 17, pp. 2503-2516
Morris, A. J., Tolan, D. R., Site-directed mutagenesis identifies aspartate 33 as a previously unidentified critical residue in the catalytic mechanism of rabbit aldolase A (1993) J. Biol. Chem., 268, pp. 1095-1110
Berman, H. M., Bhat, T. N., Bourne, P. E., Feng, Z., Gilliland, G., Weissig, H., Westbrook, J., The Protein Data Bank and the challenge of structural genomics (2000) Nat. Struct. Biol., 7, pp. 957-959
Gamblin, S. J., Davies, G. J., Grimes, J. M., Jackson, R. M., Littlechild, J. A., Watson, H. C., Activity and specificity of human aldolases (1991) J. Mol. Biol., 219, pp. 573-576
Choi, K. H., Mazurkie, A. S., Morris, A. J., Utheza, D., Tolan, D. R., Allen, K. N., Structure of a fructose-1, 6-bis (phosphate) aldolase liganded to its natural substrate in a cleavage-defective mutant at 2. 3 (1999) Biochemistry, 38, pp. 12655-12664
Choi, K. H., Shi, J., Hopkins, C. E., Tolan, D. R., Allen, K. N., Snapshots of catalysis: The structure of fructose-1, 6- (bis) phosphate aldolase covalently bound to the substrate dihydroxyacetone phosphate (2001) Biochemistry, 40, pp. 13868-13875
Hutchinson, E. G., Thornton, J. M., PROMOTIF - A program to identify and analyse structural motifs in proteins (1996) Protein Sci., 5, pp. 212-220
Jones, T. A., Kjeldgaard, M., Electron-density map interpretation (1997) Methods Enzymol., 277, pp. 173-208
Laskowski, R. A., MacArthur, M. W., Moss, D. S., Thornton, J. M., PROCHECK: A program to check the stereochemical quality of protein structures (1993) J. Appl. Crystallogr., 26, pp. 283-291
Kraulis, P. J., MolScript: A program to produce both detailed and schematic plots of protein structures (1991) J. Appl. Crystallogr., 24, pp. 945-949
Merritt, E. A., Bacon, D. J., Raster3D: Photorealistic molecular graphics (1997) Methods Enzymol., 277, pp. 505-524
Minakami, S. Y., Oshikawa, H., Thermodynamic considerations on erythrocyte glycolysis (1965) Biochem. Biophys. Res. Commun., 18, pp. 345-349
Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function
We have identified a new mutation in the FBP (fructose 1,6-bis-phosphate) aldolase A gene in a child with suspected haemolytic anaemia associated with myopathic symptoms at birth and with a subsequent diagnosis of arthrogryposis multiplex congenita and pituitary ectopia. Sequence analysis of the whole gene, also performed on the patient's full-length cDNA, revealed only a Gly(346) --> Ser substitution in the heterozygous state. We expressed in a bacterial system the new aldolase A Gly(346) --> Ser mutant, and the Glu(206) --> Lys mutant identified by others, in a patient with an aldolase A deficit. Analysis of their functional profiles showed that the Gly(346) --> Ser mutant had the same K-m as the wild-type enzyme, but a 4-fold lower k(cat). The Glu(206) --> Lys mutant had a K-m approx. 2-fold higher than that of both the Gly(346) --> Ser mutant and the wild-type enzyme, and a k(cat) value 40 % less than the wild-type. The Gly(346) --> Ser and wild-type enzymes had the same T-m (melting temperature), which was approx. 6-7 degreesC higher than that of the Glu(206) --> Lys enzyme. An extensive molecular graphic analysis of the mutated enzymes, using human and rabbit aldolase A crystallographic structures, suggests that the Glu(206) --> Lys mutation destabilizes the aldolase A tetramer at the subunit interface, and highlights the fact that the glycine-to-serine substitution at position 346 limits the flexibility of the C-terminal region. These results also provide the first evidence that Gly(346) is crucial for the correct conformation and function of aldolase A, because it governs the entry/release of the substrates into/from the enzyme cleft, and/or allows important C-terminal residues to approach the active site.
We have identified a new mutation in the FBP (fructose 1,6-bis-phosphate) aldolase A gene in a child with suspected haemolytic anaemia associated with myopathic symptoms at birth and with a subsequent diagnosis of arthrogryposis multiplex congenita and pituitary ectopia. Sequence analysis of the whole gene, also performed on the patient's full-length cDNA, revealed only a Gly(346) --> Ser substitution in the heterozygous state. We expressed in a bacterial system the new aldolase A Gly(346) --> Ser mutant, and the Glu(206) --> Lys mutant identified by others, in a patient with an aldolase A deficit. Analysis of their functional profiles showed that the Gly(346) --> Ser mutant had the same K-m as the wild-type enzyme, but a 4-fold lower k(cat). The Glu(206) --> Lys mutant had a K-m approx. 2-fold higher than that of both the Gly(346) --> Ser mutant and the wild-type enzyme, and a k(cat) value 40 % less than the wild-type. The Gly(346) --> Ser and wild-type enzymes had the same T-m (melting temperature), which was approx. 6-7 degreesC higher than that of the Glu(206) --> Lys enzyme. An extensive molecular graphic analysis of the mutated enzymes, using human and rabbit aldolase A crystallographic structures, suggests that the Glu(206) --> Lys mutation destabilizes the aldolase A tetramer at the subunit interface, and highlights the fact that the glycine-to-serine substitution at position 346 limits the flexibility of the C-terminal region. These results also provide the first evidence that Gly(346) is crucial for the correct conformation and function of aldolase A, because it governs the entry/release of the substrates into/from the enzyme cleft, and/or allows important C-terminal residues to approach the active site.
Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function
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Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function
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Andreotti G, Pedone E, Giordano A, Cubellis MV
* Biochemical phenotype of a common disease-causing mutation and a possible therapeutic approach for the phosphomannomutase 2-associated disorder of glycosylation (265 views)
Molecular Genetics & Genomic Medicine (ISSN: 2324-9269), 2013 May; 1(1): 32-44.
Impact Factor: 2.082
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Esposito G, Vitagliano L, Cevenini A, Amelio T, Zagari A, Salvatore F
* Unraveling the structural and functional features of an aldolase A mutant involved in the hemolytic anemia and severe rhabdomyolysis reported in a child (411 views)
Haematologica (ISSN: 0006-4971, 0006-6497, 0390-6078), 2005 Jan 15; 105(2): 905-906.
Impact Factor: 10.131
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* Biochemical phenotype of a common disease-causing mutation and a possible therapeutic approach for the phosphomannomutase 2-associated disorder of glycosylation (265 views)
Molecular Genetics & Genomic Medicine (ISSN: 2324-9269), 2013 May; 1(1): 32-44.
Impact Factor: 2.082
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Esposito G, Vitagliano L, Cevenini A, Amelio T, Zagari A, Salvatore F
* Unraveling the structural and functional features of an aldolase A mutant involved in the hemolytic anemia and severe rhabdomyolysis reported in a child (411 views)
Haematologica (ISSN: 0006-4971, 0006-6497, 0390-6078), 2005 Jan 15; 105(2): 905-906.
Impact Factor: 10.131
View Export to BibTeX Export to EndNote
2 Records (2 excluding Abstracts).
Total impact factor: 12.213 (12.213 excluding Abstracts).
Total 5 year impact factor: 11.855 (11.855 excluding Abstracts).
Total impact factor: 12.213 (12.213 excluding Abstracts).
Total 5 year impact factor: 11.855 (11.855 excluding Abstracts).
378 views. Last view on Saturday 14 January 2023, 17:31:50
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