Mass spectrometric analysis of asparagine deamidation and aspartate isomerization in polypeptides.
One of the most frequent modifications in proteins and peptides is the deamidation of asparagine, a spontaneous non-enzymatic reaction leading to a mixture of L,D-succinimidyl, L,D-aspartyl, and L,D-isoaspartyl forms, with L-isoaspartyl dominating. Spontaneous isomerization of L-Asp yields the same products. In vivo, these unusual forms of aspartate are repaired by the protein L-isoaspartyl O-methyltransferase enzyme, with the balance between isomerization and repair affecting the organism physiology. Mass spectrometric analysis of this balance involves isomer separation, iso-Asp/Asp quantification, and iso-Asp site identification. This review highlights the issues associated with these steps and discusses the prospects of high-throughput iso-Asp analysis.
Yang
Hongqian
H
Division of Molecular Biometry, Department of Medicinal Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Zubarev
Roman A
RA
D000577:Amides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001216:Asparagine / Q000737:chemistry* / Q000378:metabolism; D001224:Aspartic Acid / Q000737:chemistry* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007536:Isomerism; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D040901:Proteomics / Q000379:methods*
D000577:Amides; D001224:Aspartic Acid; D001216:Asparagine
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