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Molecular Clocks

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Specialty Science
Date 2001 Feb 7
PMID 11158575
Citations 138
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Abstract

A convenient and precise mass spectrometric method for measurement of the deamidation rates of glutaminyl and asparaginyl residues in peptides and proteins has been developed; the rates of deamidation of 306 asparaginyl sequences in model peptides at pH 7.4, 37.0 degrees C, 0.15 M Tris.HCl buffer have been determined; a library of 913 amide-containing peptides for use by other investigators in similar studies has been established; and, by means of simultaneous deamidation rate measurements of rabbit muscle aldolase and appropriate model peptides in the same solutions, the use of this method for quantitative measurement of the relative effects of primary, secondary, tertiary, and quaternary protein structure on deamidation rates has been demonstrated. The measured rates are discussed with respect to the hypothesis that glutaminyl and asparaginyl residues serve, through deamidation, as molecular timers of biological events.

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References
1.
Capasso S, Salvadori S . Effect of the three-dimensional structure on the deamidation reaction of ribonuclease A. J Pept Res. 1999; 54(5):377-82. DOI: 10.1034/j.1399-3011.1999.00111.x. View

2.
Lindner H, Sarg B, Hoertnagl B, Helliger W . The microheterogeneity of the mammalian H1(0) histone. Evidence for an age-dependent deamidation. J Biol Chem. 1998; 273(21):13324-30. DOI: 10.1074/jbc.273.21.13324. View

3.
Solstad T, Flatmark T . 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. 2000; 267(20):6302-10. DOI: 10.1046/j.1432-1327.2000.01715.x. View

4.
Flatmark T, Sletten K . Multiple forms of cytochrome c in the rat. Precursor-product relationship between the main component Cy I and the minor components Cy II and Cy 3 in vivo. J Biol Chem. 1968; 243(7):1623-9. View

5.
Robinson A, McKerrow J, Cary P . Controlled deamidation of peptides and proteins: an experimental hazard and a possible biological timer. Proc Natl Acad Sci U S A. 1970; 66(3):753-7. PMC: 283114. DOI: 10.1073/pnas.66.3.753. View