Deamidation of labile asparagine residues in the autoregulatory sequence of human phenylalanine hydroxylase: Structural and functional implications

European Journal of Biochemistry

Volumn 270, Issue 5, 2003, Pages 929-938

  Solstad, Therese ^a   Carvalho, Raquel N ^a   Andersen, Ole A ^b   Waidelich, Dietmar ^c   Flatmark, Torgeir ^a  

^a UNIVERSITY OF BERGEN   (Norway)

^b UNIVERSITY OF TROMSØ   (Norway)

^c PE Biosystems   (Germany)

Author keywords

Asparagine; Deamidation; Microheterogeneity; Phenylalanine hydroxylase; Structure and function

Indexed keywords

ASPARAGINE; GLYCINE; ISOASPARTIC ACID; PEPTIDE HISTIDINE ISOLEUCINE; PHENYLALANINE 4 MONOOXYGENASE;

ALGORITHM; ALKALINITY; AMINO ACID SEQUENCE; ARTICLE; AUTOREGULATION; CATALYSIS; COMPUTER ANALYSIS; CONFORMATION; DEAMINATION; ENZYME SUBSTRATE; GEL MOBILITY SHIFT ASSAY; HYDROPHILICITY; INCUBATION TIME; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; METHYLATION; NONHUMAN; PREDICTION; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REVERSED PHASE LIQUID CHROMATOGRAPHY; ROOM TEMPERATURE; SITE DIRECTED MUTAGENESIS; TWO DIMENSIONAL ELECTROPHORESIS;

AMIDES; ASPARAGINE; CHROMATOGRAPHY, LIQUID; ELECTROPHORESIS, GEL, TWO-DIMENSIONAL; HUMANS; KINETICS; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; PHENYLALANINE HYDROXYLASE; PHOSPHORYLATION; PROTEIN CONFORMATION; SPECTROMETRY, MASS, MATRIX-ASSISTED LASER DESORPTION-IONIZATION; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037338309     PISSN: 00142956     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1432-1033.2003.03455.x     Document Type: Article

References (39)

1. Robinson, N.E. & Robinson, A.B. (2001) Molecular clocks. Proc. Natl Acad. Sci. 98, 944-949.11.
2. Robinson, A.B., McKerrow, J.H. & Cary, P. (1970) Controlled deamidation of peptides and proteins: an experimental hazard and a possible biological timer. Proc. Natl Acad. Sci. 66, 753-757.
3. McKerrow, J.H. & Robinson, A.B. (1971) Deamidation of asparaginyl residues as a hazard in experimental protein and peptide procedures. Anal. Biochem. 42, 565-568.
4. Bornstein, P. & Balian, G. (1970) The specific nonenzymatic cleavage of bovine ribonuclease with hydroxylamine. J. Biol. Chem. 245, 4854-4856.
5. Meinwald, Y.C., Stimson, E.R. & Scheraga, H.A. (1986) Deamidation of the asparaginyl-glycyl sequence. Int. J. Pept. Protein Res. 28, 79-84.
6. Geiger, T. & Clarke, S. (1987) Deamidation, isomerization, and racemization at asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation. J. Biol. Chem. 262, 785-794.
7. Aswad, D.W. (1984) Stoichiometric methylation of porcine adrenocorticotropin by protein carboxyl methyltransferase requires deamidation of asparagine. Evidence for methylation at the alpha-carboxyl group of atypical 1-isoaspartyl residues. J. Biol. Chem. 259, 10714-10721.
8. Wright, H.T. (1991) Nonenzymatic deamidation of asparaginyl and glutaminyl residues in proteins. Crit. Rev. Biochem. Mol. Biol. 26, 1-52.
9. Robinson, N.E. (2002) Protein deamidation. Proc. Natl Acad. Sci. 99, 5283-5288.
10. Robinson, N.E. & Robinson, A.B. (2001) Prediction of protein deamidation rates from primary and three-dimensional structure. Proc. Natl Acad. Sci. 98, 4367-4372.
11. Flatmark, T. (1967) Multiple molecular forms of bovine heart cytochrome c. V. A comparative study of their physicochemical properties and their reactions in biological systems. J. Biol. Chem. 242, 2454-2459.
12. Robinson, N.E. & Robinson, A.B. (2001) Deamidation of human proteins. Proc. Natl Acad. Sci. 98, 12409-12413.
13. Solstad, T. & Flatmark, T. (2000) Microheterogeneity of recombinant human phenylalanine hydroxylase as a result of nonenzymatic deamidations of labile amide containing amino acids. Effects on catalytic and stability properties. Eur. J. Biochem. 267, 6302-6310.
14. Carvalho, R.M.N., Solstad, T., Robinson, N.E., Robinson, A.B. & Flatmark, T. (2002) Possible contributions of labile asparqine residues to differences in regulatory properties of human and rat phenylalanine hydroxylase. In Chemistry and Biology of Pteridines and Folates (Milstien, S., Kapatos, G., Levine, R.A. & Shane, B., eds), pp. 103-107, Kluwer Academic Publishers, Boston.
15. Kobe, B., Jennings, I.G., House, C.M., Michell, B.J., Goodwill, K.E., Santarsiero, B.D., Stevens, R.C., Cotton, R.G. & Kemp, B.E. (1999) Structural basis of autoregulation of phenylalanine hydroxylase. Nat. Struct. Biol. 6, 442-448.
16. Eiken, H.G., Knappskog, P.M., Apold, J. & Flatmark, T. (1996) PKU mutation G46S is associated with increased aggregation and degradation of the phenylalanine hydroxylase enzyme. Hum. Mutat. 7, 228-238.
17. Erlandsen, H., Bjørgo, E., Flatmark, T. & Stevens, R.C. (2000) Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase. Biochemistry 39, 2208-2217.
18. Martínez, A., Knappskog, P.M., Olafsdottir, S., Døskeland, A.P., Eiken, H.G., Svebak, R.M., Bozzini, M., Apold, J. & 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. Biochem. J. 306, 589-597.
19. 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 non-specific cleavage of the fusion protein by restriction protease. Biochem. J. 313, 409-414.
20. Laemmli, U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227, 680-685.
21. Wehofsky, M., Hoffmann, R. & Hubert, M. (2001) Isotopic deconvolution of matrix-assisted laser desorption/ionization mass spectra for substance-class specific analysis of complex samples. Eur. J. Mass Spectrom. 7, 39-46.
22. LiCata, V.J. & Allewell, N.M. (1997) Is substrate inhibition a consequence of allostery in aspartate transcarbamylase? Biophys. Chem. 64, 225-234.
23. Bjorgo, 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: contribution of the flexible hinge region Asp425-Gln429 to the tetramerization and cooperative substrate binding. Eur. J. Biochem. 268, 997-1005.
24. Døskeland, A.P. & Flatmark, T. (1996) Recombinant human phenylalanine hydroxylase is a substrate for the ubiquitin-conjugating enzyme system. Biochem. J. 319, 941-945.
25. Kosky, A.A., Razzaq, U.O., Treuheit, M.J. & Brems, D.N. (1999) The effects of alpha-helix on the stability of Asn residues: deamidation rates in peptides of varying helicity. Protein Sci. 8, 2519-2523.
26. Døskeland, A.P., Schworer, C.M., Døskeland, S.O., Chrisman, T.D., Soderling, T.R., Corbin, J.D. & Flatmark, T. (1984) Some aspects of the phosphorylation of phenylalanine 4-mono-oxygenase by a calcium-dependent and calmodulin-dependent protein kinase. Eur. J. Biochem. 145, 31-37.
27. Flatmark, T. (1966) On the heterogeneity of beef heart cytochrome c. A kinetic study of the non-enzymatic deamidation of the main subfractions (Cy I-Cy III). Acta Chem. Scand. 20, 1487-1496.
28. Freitag, C. & Clarke, S. (1981) Reversible methylation of cytoskeletal and membrane proteins in intact human erythrocytes. J. Biol. Chem. 256, 6102-6108.
29. O'Connor, C.M. & Clarke, S. (1984) Carboxyl methylation of cytosolic proteins in intact human erythrocytes. Identification of numerous methyl-accepting proteins including hemoglobin and carbonic anhydrase. J. Biol. Chem. 259, 2570-2578.
30. Johnson, B.A. & Aswad, D.W. (1991) Optimal conditions for the use of protein l-isoaspartyl methyltransferase in assessing the isoaspartate content of peptides and proteins. Anal. Biochem. 192, 384-391.
31. Wright, H.T. (1991) Sequence and structure determinants of the nonenzymatic deamidation of asparagine and glutamine residues in proteins. Protein Eng. 4, 283-294.
32. Clarke, S. (1987) Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins. Int. J. Pept. Protein. Res. 30, 808-821.
33. Aswad, D.W., Paranandi, M.V. & Schurter, B.T. (2000) Isoaspartate in peptides and proteins: formation, significance, and analysis. J. Pharm. Biomed. Anal. 21, 1129-1136.
34. Tyler-Cross, R. & Schirch, V. (1991) Effects of amino acid sequence, buffers, and ionic strength on the rate and mechanism of deamidation of asparagine residues in small peptides. J. Biol. Chem. 266, 22549-22556.
35. Johnson, B.A., Langmack, E.L. & Aswad, D.W. (1987) Partial repair of deamidation-damaged calmodulin by protein carboxyl methyltransferase. J. Bio. Chem. 262, 12283-12287.
36. Jennings, I.G., Cotton, R.G. & Kobe, B. (2000) Functional analysis, using in vitro mutagenesis, of amino acids located in the phenylalanine hydroxylase active site. Arch. Biochem. Biophys. 384, 238-244.
37. Miranda, F.F., Teigen, K., Thórólfsson, M., Svebak, R.M., Knappskog, P.M., Flatmark, T. & Martínez, A. (2002) Phosphorylation and mutations of Ser16 in human phenylalanine hydroxylase. Kinetic and structural effects. J. Biol. Chem. 277, 40937-40943.
38. Kraulis, P.J. (1991) MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallog. 24, 946-950.
39. Carvalho, R.N., Solstad, T., Bjørgo, E., Barroso, J.F. & Flatmark, T. (2003) Deamidations in recombinant human phenylalanine hydroxylase. Identification of labile asparagine residues and functional characterization of Asn→Asp mutant forms. J. Biol. Chem., in press.