Origin of the Selectivity of α‐Dicarbonyl Reagents for Arginyl Residues of Anion‐Binding Sites

László PATTHY, János THÉSZ

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Factors affecting the reactivity of arginyl side‐chains of proteins toward α‐dicarbonyl reagents have been considered. The reaction of the guanidino group with different α‐dicarbonyl compounds is shown to proceed by a common pathway, the rate‐limiting step being essentially identical with an amine–carbonyl addition reaction. We found that the protonated guanidino group is the main reacting species in acidic solutions; at neutral–alkaline pH, however, reaction of the unprotonated form is predominant. Under the conditions usually employed for the modification of enzymes only the pathway utilizing the unprotonated form of arginine is of importance, the reactivity of individual arginyl side‐chains toward α‐dicarbonyls is primarily determined by the pka value of the guanidinium groups. It is proposed that the pKa value of arginyl residues of anion binding sites is lower than that of other arginyl residues, due to the strong positive electric potential of the anion binding sites. The lower pKa of arginine leads to its hyperreactivity toward the different α‐dicarbonyl reagents, providing an explanation for the general observation that α‐dicarbonyl reagents are remarkably selective for arginyl residues involved in anion binding. The various predictions of our proposition are considered and tested experimentally on the arginine residue of the high‐affinity anion binding site of rabbit muscle aldolase.

Original languageEnglish
Pages (from-to)387-393
Number of pages7
JournalEuropean Journal of Biochemistry
Volume105
Issue number2
DOIs
Publication statusPublished - Apr 1980

ASJC Scopus subject areas

  • Biochemistry

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