The chemical basis of protein splicing

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Abstract
Protein splicing is a recently discovered mechanism for the post-translational processing of proteins. It involves the self-catalyzed excision of an intervening polypeptide, the intein, from an inactive enzyme precursor and the formation of an active enzyme by joining the flanking regions by a peptide bond. Protein splicing occurs at a catalytic center that resides entirely within the intein. The catalyzed reactions include rearrangement of a peptide bond adjacent to cysteine or serine to yield a peptide ester, intramolecular transesterification involving a second cysteine, serine, or threonine side chain to yield a branched protein, and cyclization of an asparagine residue coupled to peptide bond cleavage to effect intein excision. This review discusses the mechanisms of these reactions and of similar reactions that underlie other types of protein rearrangements as well as the current state of knowledge on how these reactions are catalyzed.