Emiko Okamura - Kinetics of the competitive reactions of isomerization and peptide bond cleavage at L-α- and D-β-aspartyl residues in an αA-crystallin fragment

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      Publication Details (including relevant citation   information):

      Aki, K. and Okamura, E. J. Pept.Sci.2017;23:2837

      Abstract:

      D-β-aspartyl(Asp)residuehasbeenfoundinalivingbodysuchasagedlenscrystallin,althoughL-α-aminoacidsareconstituentsin  naturalproteins.IsomerizationfromL-α-toD-β-Aspprobablymodulatesstructurestoaffectbiochemicalreactions.AtAspresidue,  isomerizationandpeptidebondcleavagecompetewitheachother.Togaininsightintohowfasteachreactionproceeds,theanalysisrequirestheconsiderationofbothpathwayssimultaneouslyandindependently.Noinformationhasbeenprovided,however, aboutthesecompetitiveprocessesbecauseeachreactionhasbeenstudiedseparately.ThecontributionofAspisomerstotherespectivepathwayshasstillbeenveiled.Inthiswork,thetwocompetitivereactions,isomerizationandspontaneouspeptidebond cleavageatAspresidue,weresimultaneouslyobservedandcomparedinanαA-crystallinfragment,S51LFRTVLD58SG60 containingL-α-andD-β-Asp58isomers.ThekineticsshowedthattheformationofL-andD-succinimide(Suc)intermediate,asafirst  stepofisomerization,wascomparableatL-α-andD-β-Asp.AlthoughL-SucwasconvertedtoL-β-Asp,D-Sucwasliabletoreturntothe originalD-β-Asp,thereversereactionmarkedenoughtoconsiderD-β-Aspasapparentlystable.D-β-Aspwasalsoresistanttothepeptidebondcleavage.SuchapparentlessreactivityisprobablythereasonforgradualandabnormalaccumulationofD-β-Aspinaliving
      bodyunderphysiologicalconditions.

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