HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aswad, D. W. Search for Related Content PubMed PubMed Citation Articles by Aswad, D. W. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 259, Issue 17, 10714-10721, Sep, 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

DW Aswad

The enzymatic methylation of porcine adrenocorticotropin (ACTH) in both its native form and a form which is deamidated at asparagine 25 has been compared using purified protein carboxyl methyltransferase from bovine brain. Incubation of deamidated ACTH with high concentrations of methyltransferase resulted in near stoichiometric levels of methyl incorporation (78 mol %), while the methylation of native ACTH was highly substoichiometric (3-12 mol %). The Km and Vmax for deamidated ACTH were 1.9 microM and 11,200 pmol/min/mg, respectively, making this peptide the most specific substrate known for the mammalian methyltransferase. Deamidation of asparagine 25 leads to the formation of an atypical isopeptide bond in which the resulting aspartyl residue is linked to the adjacent glycine 26 via its side-chain beta-carboxyl group rather than the usual alpha-carboxyl linkage (Graf, L., Bajusz, S., Patthy A., Barat, E., and Cseh, G. (1971) Acta Biochim. Biophys. Acad. Sci. Hung. 6, 415-418; Bornstein, P., and Balian, G. (1977) Methods Enzymol. 47, 132-145). A synthetic isopeptide (beta-linked) analog of deamidated ACTH serves as a highly effective substrate for the methyltransferase, but the corresponding normal (alpha-linked) peptide does not, indicating that this enzyme selectively recognizes the alpha-carboxyl group of atypical beta-linked L-aspartyl residues (see also accompanying paper (Murray, E.D., Jr., and Clarke, S. (1984) J. Biol. Chem. 259, 10722-10732]. Methylation of atypical beta-linked L- aspartyl residues resulting from deamidation can account for previous observations that in vitro protein carboxyl methylation in mammalian systems almost always occurs with a low stoichiometry and that these protein methyl esters are considerably less stable than most chemically formed protein methyl esters.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Curnis, R. Longhi, L. Crippa, A. Cattaneo, E. Dondossola, A. Bachi, and A. Corti Spontaneous Formation of L-Isoaspartate and Gain of Function in Fibronectin J. Biol. Chem., November 24, 2006; 281(47): 36466 - 36476. [Abstract] [Full Text] [PDF]

				J. X. Zhu, H. A. Doyle, M. J. Mamula, and D. W. Aswad Protein Repair in the Brain, Proteomic Analysis of Endogenous Substrates for Protein L-Isoaspartyl Methyltransferase in Mouse Brain J. Biol. Chem., November 3, 2006; 281(44): 33802 - 33813. [Abstract] [Full Text] [PDF]

				K. Chourey, M. R. Thompson, J. Morrell-Falvey, N. C. VerBerkmoes, S. D. Brown, M. Shah, J. Zhou, M. Doktycz, R. L. Hettich, and D. K. Thompson Global Molecular and Morphological Effects of 24-Hour Chromium(VI) Exposure on Shewanella oneidensis MR-1 Appl. Envir. Microbiol., September 1, 2006; 72(9): 6331 - 6344. [Abstract] [Full Text] [PDF]

				K. J. Reissner, M. V. Paranandi, T. M. Luc, H. A. Doyle, M. J. Mamula, J. D. Lowenson, and D. W. Aswad Synapsin I Is a Major Endogenous Substrate for Protein L-Isoaspartyl Methyltransferase in Mammalian Brain J. Biol. Chem., March 31, 2006; 281(13): 8389 - 8398. [Abstract] [Full Text] [PDF]

				G. W. Young, S. A. Hoofring, M. J. Mamula, H. A. Doyle, G. J. Bunick, Y. Hu, and D. W. Aswad Protein L-Isoaspartyl Methyltransferase Catalyzes in Vivo Racemization of Aspartate-25 in Mammalian Histone H2B J. Biol. Chem., July 15, 2005; 280(28): 26094 - 26098. [Abstract] [Full Text] [PDF]

				R. Pepperkok, A. Hotz-Wagenblatt, N. Konig, A. Girod, D. Bossemeyer, and V. Kinzel Intracellular Distribution of Mammalian Protein Kinase A Catalytic Subunit Altered by Conserved Asn2 Deamidation J. Cell Biol., February 21, 2000; 148(4): 715 - 726. [Abstract] [Full Text] [PDF]

				A. Yamamoto, H. Takagi, D. Kitamura, H. Tatsuoka, H. Nakano, H. Kawano, H. Kuroyanagi, Y.-i. Yahagi, S.-i. Kobayashi, K.-i. Koizumi, et al. Deficiency in Protein L-Isoaspartyl Methyltransferase Results in a Fatal Progressive Epilepsy J. Neurosci., March 15, 1998; 18(6): 2063 - 2074. [Abstract] [Full Text] [PDF]

				A. Kossiakoff Tertiary structure is a principal determinant to protein deamidation Science, April 8, 1988; 240(4849): 191 - 194. [Abstract] [PDF]

				A. L. Young, W. G. Carter, H. A. Doyle, M. J. Mamula, and D. W. Aswad Structural Integrity of Histone H2B in Vivo Requires the Activity of Protein L-Isoaspartate O-Methyltransferase, a Putative Protein Repair Enzyme J. Biol. Chem., September 28, 2001; 276(40): 37161 - 37165. [Abstract] [Full Text] [PDF]

				N. Thapar, S. C. Griffith, T. O. Yeates, and S. Clarke Protein Repair Methyltransferase from the Hyperthermophilic Archaeon Pyrococcus furiosus. UNUSUAL METHYL-ACCEPTING AFFINITY FOR D-ASPARTYL AND N-SUCCINYL-CONTAINING PEPTIDES J. Biol. Chem., January 4, 2002; 277(2): 1058 - 1065. [Abstract] [Full Text] [PDF]