Initiation of the reaction of deamidation in triosephosphate isomerase: investigations by means of molecular dynamics simulations

The Journal of Physical Chemistry. B
Ilke UgurGerald Monard

Abstract

Deamidation of asparagine is the spontaneous degradation of this residue into aspartic acid. The kinetics of this slow reaction is mainly dependent on the nature of the adjacent amino acid that follows asparagine in a peptide or protein primary sequence. In the homodimer triosephosphate isomerase (TPI), there are two main deamidation sites per subunit: Asn15-Gly16 and Asn71-Gly72 for which deamidation dynamics are known to be interrelated. In this study, we investigate the initiation of the deamidation reaction in TPI by means of molecular dynamics. Simulations based on classical AMBER force field are performed in a 60 to 90 ns time scale for six distinct samples. Conformational changes, desolvation effects, and hydrogen bond networks are analyzed to interpret the experimental findings and previous quantum mechanical (QM) results. Results that are based on desolvation analysis clarify the assignments in the literature about the different behaviors of two deamidating sites in TPI. Conformational analysis supports findings suggested by QM studies: the most favorable reaction mechanism is the one that yields to succinimide intermediate via one or two step routes. The mechanism leading to the succinimide intermediate most likely in...Continue Reading

References

Aug 1, 1986·Archives of Biochemistry and Biophysics·K U Yüksel, R W Gracy
Jul 1, 1986·International Journal of Peptide and Protein Research·Y C MeinwaldH A Scheraga
Jan 1, 1974·Current Topics in Cellular Regulation·A B Robinson, C J Rudd
Nov 28, 1973·Journal of the American Chemical Society·A B RobinsonJ H McKerrow
Mar 1, 1970·Journal of Molecular Biology·S B Needleman, C D Wunsch
Oct 1, 1981·Mechanisms of Ageing and Development·P M YuanR W Gracy
Nov 24, 1999·The Journal of Peptide Research : Official Journal of the American Peptide Society·S Capasso, S Salvadori
Feb 7, 2001·Proceedings of the National Academy of Sciences of the United States of America·N E Robinson, A B Robinson
Apr 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·N E Robinson, A B Robinson
Jan 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Gerwald JoglLiang Tong
Apr 6, 2004·Mechanisms of Ageing and Development·Steven J Weintraub, Scott R Manson
May 14, 2004·The Journal of Peptide Research : Official Journal of the American Peptide Society·N E RobinsonA B Robinson
May 14, 2004·The Journal of Peptide Research : Official Journal of the American Peptide Society·N E Robinson, A B Robinson
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Apr 19, 2006·Biochemistry·Baron Peters, Bernhardt L Trout
Jul 11, 2006·The Journal of Physical Chemistry. a·Saron CatakManuel F Ruiz-López
Jan 15, 2008·Biochemistry·Sertan Cansu, Pemra Doruker
Aug 22, 2008·The Journal of Physical Chemistry. a·Saron CatakManuel F Ruiz-López
Jan 20, 2009·The Journal of Physical Chemistry. a·Saron CatakManuel F Ruiz-López
Aug 10, 2010·Cellular and Molecular Life Sciences : CMLS·R K WierengaR Venkatesan

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