Endopeptidases and prohormone processing

Peptide hormones and peptide transmitters are generated from polypeptide precursors by specific cleavage reactions which take place principally at sites formed by single or paired basic residues. Not all the possible cleavage sites are utilised, however, and the degree of processing of many propeptides has been found to vary according to the tissue of origin. The restricted nature of processing reactions could point to the existence of a series of enzymes with stringent specificities, recognising regions of structure in addition to the single or paired basic residues. Alternatively the action of processing enzymes may be directed by conformation of the pro-peptide which could focus the action of a protease onto or away from a particular site. In addition certain post-translational modifications such as glycosylation or phosphorylation may influence the accessibility of a site to the approach of a processing enzyme. In this review we describe recent advances that have been made in the characteristization of proteolytic processing enzymes, we examine the relevance of the various factors that could account for restricted processing and discuss new approaches that may lead to better understanding of the mechanisms involved.