Protein‐Derived Cofactors

Abstract

Protein‐derived cofactors are catalytic or redox‐active centres in proteins that are formed by covalent irreversible posttranslational modification of one or more amino acid residues. The mechanisms by which these posttranslational modifications are catalysed are quite diverse. In some cases, these modifications occur autocatalytically, and in other cases, they are enzyme catalysed. The formation of protein‐derived cofactors expands the range of chemical reactions that may be catalysed by enzymes in the absence of exogenous metal or organic cofactors. Protein‐derived cofactors typically function as electrophiles in catalysis and sometimes stabilise free‐radical intermediates or mediate biological electron transfer. This article describes the structures and functions of several protein‐derived cofactors and the diverse mechanisms of posttranslational modification through which they are generated. Key Concepts: Protein‐derived cofactors are formed by irreversible posttranslational modification of amino acid residues. Protein‐derived cofactors typically serve as electrophiles or stabilise free radicals during enzyme catalysis. Amino acid residues may acquire new catalytic or redox functions from posttranslational modification. Modification of amino acids that provide ligands for metals can alter the properties of metalloenzymes. Protein‐derived cofactors may be formed by a variety of autocatalytic and enzyme‐catalysed processes.