Abstract
Enzymes have been detected in all cells examined so far that catalyze the incorporation of methyl groups from S-adenosylmethionine into base-labile linkages on proteins. Although the products of these reactions have many of the properties of methyl esters, their frequent instability has often precluded direct analysis of the linkage chemistry. As a result, previous studies of “protein carboxyl methyltransferase” have included representatives of what has turned out to be at least two distinct classes of enzymes. The often mentioned specificity of such an activity for aspartyl and glutamyl residues is based largely on the apparent chemical reasonableness of such assignments, and specific evidence for the methylation of such residues has rarely been presented. The lack of specific knowledge on the chemistry of such modification reactions has been accompanied by a similar lack of understanding of their physiological role (for reviews of the earlier literature see Gagnon and Heisler, 1979; Borchardt, 1980; Paik and Kim, 1980; O’Dea et al., 1981; Clarke, 1985).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ahern, T. J., and Klibanov, A. M., 1985, The mechanism of irreversible enzyme inactivation at 100°C, Science, 228:1280.
Ahern, T. J., Casal, J. I., Petsko, G. A., and Klibanov, A. M., 1987, Control of oligomeric enzyme thermostability by protein engineering, Proc. Natl. Acad. Sci. U. S. A., 84:675.
Altman, G., 1986, Presence of D-aspartic acid and D-aspartyl peptides in human urine: Implications for protein racemization and turnover, Master’s Thesis, Department of Chemistry and Biochemistry, University of California at Los Angeles.
Aswad, D. W., 1984, Stoichiometric methylation of porcine adrenocorticotropin by protein carboxyl methyltransferase requires deamidation of asparagine 25: Evidence for methylation at the alpha-carboxyl group of atypical L-isoaspartyl residues, J. Biol. Chem., 259:10714.
Aswad, D. W., and Deight, E. A., 1983, Purification and characterization of two distinct isozymes of protein carboxymethylase from bovine brain, J. Neurochem., 40:1718.
Aswad, D. W., and Johnson, B. A., 1987, The unusual substrate specificity of eukaryotic protein carboxyl methyltransferases, Trends Biochem. Sci., 12:155.
Bachmair, A., Finley, D., and Varshavsky, A., 1986, In vivo half-life of a protein is a function of its amino-terminal residue, Science, 234:179.
Bada, J. L., 1984, In vivo racemization in mammalian proteins, Methods Enzvmol., 106:98.
Barber, J. R., and Clarke, S., 1983, Membrane protein carboxyl methylation increases with human erythrocyte age: Evidence for an increase in the number of methylatable sites, J. Biol. Chem., 258:1189.
Barber, J. R., and Clarke, S., 1985, Demethylation of protein carboxyl methyl esters: A nonenzymatic process in human erythrocytes?, Biochemistry, 24:4867.
Bernhard, S. A., 1983, Nucleophilic displacement reactions at ester and thioester bonds, Annals N. Y. Acad. Sci., 421:28.
Betz, R., Crabb, J. W., Meyer, H. E., Wittig, R., and Duntze, W., 1987, Amino acid sequences of a-Factor mating peptides from Saccharomyces cerevisiae, J. Biol. Chem., 262:546.
Blodgett, J. K., Loudon, G. M., and Collins, K. D., 1985, Specific cleavage of peptides containing an aspartic acid beta-hydroxamic acid residue, J. Am. Chem. Soc., 197:4305.
Borchardt, R. T., 1980, S-Adenosyl-L-methionine-dependent macromolecule methyltransferases, J. Med. Chem., 23:347.
Bornstein, P., and Balian, G., 1970, The specific nonenzymatic cleavage of bovine ribonuclease with hydroxylamine, J. Biol. Chem., 245:4854.
Brot, N. and Weissbach, H., 1983, Biochemistry and physiological role of methionine sulfoxide residues in proteins, Arch. Biochem. Biophys., 223:271.
Brunauer, L. S., and Clarke, S., 1986, Age-dependent accumulation of protein residues which can be hydrolyzed to D-aspartic acid in human erythrocytes” J. Biol. Chem., 261:12538.
Chen, J.-K., and Liss, M., 1978, Evidence of carboxyraethylation of nascent peptide chains on ribosomes, Biochem. Biophys. Res. Commun., 84:261.
Chen, Z.-Q., Ulsh, L. S., DuBois, G., and Shin, T. Y., 1985, Post-translational processing of p21 ras proteins involves palmitoylation of the C-terminal tetrapeptide containing cysteine-186, J. Virology, 56:607.
Clarke, S., 1985, Protein carboxyl methyltransferases: Two distinct classes of enzymes, Annu. Rev. Biochem., 54:479.
Clarke, S., 1987, Propensity for spontaneous succinimide formation from aspartyl and asparaginyl residues in cellular proteins, submitted for publication.
Clarke, S., McFadden, P. N., O’Connor, C. M., and Lou, L. L., 1984, Isolation of D-aspartic acid beta-methyl ester from erythrocyte carboxyl methylated proteins, Methods Enzvmol., 106:331.
Clarke, S., Panasenko S., Sparrow, K., and Koshland, D. E. Jr., 1980, In vitro methylation of bacterial Chemotaxis proteins: Characterization of protein methyltransferase activity in crude extracts of Salmonella typhimurium, J. Supramol. Struct., 13:315.
Di Donato, A., Galletti, P., and D’Alessio, G., 1986, Selective deamidation and enzymatic methylation of seminal ribonuclease, Biochemistry, 25:8361.
Diliberto, E. J., Jr., and Axelrod, J., 1976, Regional and subcellular distribution of carboxymethylase in brain and other tissues, J. Neurochem., 26:1159.
Flatmark, T., 1966, On the heterogeneity of beef heart cytochrome c: III. A kinetic study of the non-enzymatic deamidation of the main subfractions (Cy I — Cy III), Acta Chem. Scand., 20:1487.
Freitag, C. and Clarke S., 1981, Reversible methylation of cytoskeletal and membrane proteins in intact human erythrocytes, J. Biol. Chem., 256:6102.
Gagnon, C., and Heisler, S., 1979, Protein carboxyl-methylation: Role in exocytosis and Chemotaxis, Life Sci., 25:993.
Galletti, P., Ingrosso, D., Iardino, P., Manna, C., Pontoni, G., and Zappia, V., 1986, Enzymatic basis for the calcium-induced decrease of membrane protein methyl esterification in intact erythrocytes: Evidence for an impairment of S-adenosylmethionine synthesis, Eur. J. Biochem.. 154:489.
Galletti, P., Ingrosso, D., Nappi, A., Gragnaniello, V., Iolascon, A., Pinto, L., 1983, Increased methyl esterification of membrane proteins in aged red blood cells: Preferential esterification of ankyrin and Band 4.1 cytoskeletal proteins, Eur. J. Biochem., 135:25.
Geiger, T. and 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.
Ishibashi, Y., Sakagami, Y., Isogai, A., and Suzuki, XT, 1984, Tremergogens A-9291-I and A-9291-VIII: Peptidyl sex hormones of Tremella brasiliensis, Biochemistry, 23:1399.
Johnson, B. A., and Aswad, D. W., 1985, Enzymatic protein carboxyl methylation at physiological pH: Cyclic imide formation explains rapid methyl turnover, Biochemistry, 24:2581.
Johnson, B. A., Freitag, N. E., and Aswad, D. W., 1985, Protein carboxyl methyltransferase selectively modifies an atypical form of calmodulin: Evidence for methylation at deamidated asparagine residues, J. Biol. Chem., 260:10913.
Johnson, B. A., Murray, E. D., Jr., Clarke, S., Glass, D. B., and Aswad, D. W., 1987a, Protein carboxyl methyltransferase facilitates conversion of atypical L-isoaspartyl peptides to normal L-aspartyl peptides, J. Biol. Chem., 262:5622.
Johnson, B. A., Langmack, E. L., and Aswad, D. W., 1987b, Partial repair of deamidation-damaged calmodulin by protein carboxyl methyltransferase, J. Biol. Chem., 262:in press.
Kleene, S. J., Hobson, A. C., and Adler, J., 1979, Isolation of glutamic acid methyl ester from an Escherichia coli membrane protein involved in Chemotaxis, J. Biol. Chem., 252:3214.
Lewis, U. J., Singh, R. N. P., Bonewald, L. F., and Seavey, B. K., 1981, Altered proteolytic cleavage of human growth hormone as a result of deamidation, J. Biol. Chem., 256:11645.
Lou, L. L. and Clarke, S., 1987, Enzymatic methylation of Band 3 anion transporter in intact human erythrocytes, Biochemistry, 26:52.
Lowenson, J., and Clarke, S., 1987, Protein carboxyl methyltransferase from human erythrocytes: Substrate specificity with L-isoaspartyl and D-aspartyl-containing peptides and proteins, Fed. Proc., in press.
McFadden, P. N., and Clarke, S., 1982, Methylation at D-aspartyl residues in red cells: A possible step in the repair of aged membrane proteins, Proc. Natl. Acad. Sci. U. S. A., 79:2460.
McFadden, P. N., and Clarke, S., 1986, Chemical conversion of aspartyl peptides to isoaspartyl peptides: A method for generating new methyl-accepting substrates for the erythrocyte D-aspartyl/L-isoaspartyl protein methyltransferase, J. Biol. Chem., 261:11503.
McFadden, P. N., and Clarke, S., 1987, Conversion of isoaspartyl peptides to normal peptides: Implications for the cellular repair of aged membrane proteins, Proc. Natl. Acad. Sci. U. S. A., 84:2595.
Midelfort, C. F., and Mehler, A. H., 1972, Deamidation in vivo of an asparagine residue of rabbit muscle aldolase, J. Biol. Chem., 247:3618.
Momand, J., and Clarke, S., 1987, Rapid degradation of D- and L-succinimide peptides by a post-proline endopeptidase in human erythrocytes, submitted for publication.
Moo-Penn, W., Jue, D. L., Bechtel, K. C., Johnson, M. H., Schmidt, R. M., McCurdy, P. R., Fox, J., Bonaventura, J., Sullivan, B., and Bonaventura, C., 1976, Hemoglobin Providence: A human hemoglobin variant occurring in two forms in vivo, J. Biol. Chem., 251:7557.
Murray, E. D., Jr., and Clarke, S., 1984, Synthetic peptide substrates for the erythrocyte protein carboxyl methyltransferase: Detection of a new site of methylation at isomerized L-aspartyl residues, J. Biol. Chem., 259:10722.
Murray, E. D., Jr., and Clarke, S., 1986, Metabolism of a synthetic L-isoaspartyl-containing hexapeptide in erythrocyte extracts: Enzymatic methyl esterification is followed by nonenzymatic succinimide formation, J. Biol. Chem., 261:310.
Nemethy, G., and Scheraga, H. A., 1977, Protein folding, Quart. Rev. Biophys., 10:239.
Nowlin, D. M., Nettleton, D. O., Ordal, G. W., and Hazelbauer, G. L., 1985, Chemotactic transducer proteins of Escherichia coli exhibit homology with methyl-accepting proteins from distantly related bacteria, J. Bacteriol., 163:262.
O’Connor, C. M., 1987, Regulation and subcellular distribution of a protein methyltransferase and its damaged aspartyl substrate sites in developing Xenopus oocytes, J. Biol. Chem., 262:in press.
O’Connor, C. M., Aswad, D. W., and Clarke, S., 1984, Mammalian brain and erythrocyte carboxyl methyltransferases are similar enzymes that recognize both D-aspartyl and L-isoaspartyl residues in structurally altered protein substrates, Proc. Natl. Acad. Sci. U. S. A., 81:7757.
O’Connor, C. M., and Clarke, S., 1983, Methylation of erythrocyte membrane proteins at extracellular and intracellular D-aspartyl sites in vitro: Saturation of intracellular sites in vivo, J. Biol. Chem., 258:8485.
O’Connor, C. M., and 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.
O’Connor, C. M., and Clarke, S., 1985a, Specific recognition of altered polypeptides by widely distributed methyltransferases, Biochem. Biophys. Res. Commun., 132:1144.
O’Connor, C. M., and Clarke, S., 1985b, Analysis of erythrocyte protein methyl esters by two-dimensional gel electrophoresis under acidic separating conditions, Anal. Biochem., 148:79.
O’Dea, R. F., Viveros, O. H., Diliberto, E. J. Jr., 1981, Protein carboxymethylation — Role in the regulation of cell functions, Biochem. Pharmacol., 30:1163.
Ota, I. M., Ding, L., and Clarke, S., 1987, Methylation at specific altered aspartyl and asparaginyl residues in glucagon by the erythrocyte protein carboxyl methyltransferase, J. Biol. Chem., 262:in press.
Paik, W. K., and Kim S., 1980, “Protein Methylation,” Wiley, New York, pp. 202–231.
Sibanda, B. L., and Thornton, J. M., 1985, Beta-Hairpin families in globular proteins, Nature, 316:74.
Stock, J. and Simms, S., 1987, Methylation, demethylation, and dearaidation at glutamate residues in membrane chemoreceptor proteins, this volume.
Stock, J. and Stock, A., 1987, What is the role of receptor methylation in bacterial Chemotaxis?, Trends Biochem. Sci., 12:in press.
Svasti, J., and Milstein, C., 1972, The complete amino acid sequence of a mouse kappa light chain, Biochem. J., 128:427.
Terwilliger, T. C., and Clarke, S., 1981, Methylation of membrane proteins in human erythrocytes: Identification and characterization of polypeptides methylated in lysed cells, J. Biol. Chem., 256:3067.
Van der Werf, P., and Koshland, D. E. Jr., 1977, Identification of a gamma-glutamyl methyl ester in bacterial membrane protein involved in Chemotaxis, J. Biol. Chem., 252:2793.
Voorter, C. E. M., Mulders, J. W. M., Bloemendal, H., and de Jong, W. W., 1987, Phosphorylation and deamidation of the eye lens protein alpha-crystallin, this volume.
Wilson, J. M., Landa, L. E., Kobayashi, R, and Kelley, W. N., 1982, Human hypoxanthine-guanine phosphoribosyltransferase: Post-translational modification of the erythrocyte enzyme, J. Biol. Chem., 257:14830.
Yuan, P. M., Talent, J. M., and Gracy, R. W., 1981, Molecular basis for the accumulation of acidic isozymes of triosephosphate isomerase on aging, Mechan. Ageing Develop., 17:151.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1988 Springer Science+Business Media New York
About this chapter
Cite this chapter
Clarke, S. (1988). Perspectives on the Biological Function and Enzymology of Protein Carboxyl Methylation Reactions in Eucaryotic and Procaryotic Cells. In: Zappia, V., Galletti, P., Porta, R., Wold, F. (eds) Advances in Post-Translational Modifications of Proteins and Aging. Advances in Experimental Medicine and Biology, vol 231. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-9042-8_17
Download citation
DOI: https://doi.org/10.1007/978-1-4684-9042-8_17
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-9044-2
Online ISBN: 978-1-4684-9042-8
eBook Packages: Springer Book Archive