SPECIFICITY OF PEPSIN AND ITS DEPENDENCE ON A POSSIBLE 'HYDROPHOBICBINDING SITE'.

Abstract

THE specificity of pepsin has been extensively investigated, and the information obtained from work using synthetic di- or tri-peptides indicates that pepsin preferentially hydrolyses peptides which contain a tyrosine or phenylalanine residue1,2. However, Sanger, using the A and B chains of insulin, found that peptide linkages which did not involve tyrosine or phenylalanine were hydrolysed by pepsin3,4. Bovey and Yanari5 recently reviewed the action of pepsin on synthetic peptides and proposed several general rules. It was pointed out, however, that these rules “do not necessarily apply to the peptic digestion of proteins and large polypeptides, which is often considerably more extensive than these rules would lead one to expect”. In order to understand the action of pepsin on protein substrates, we have made a systematic examination of the sequence of amino-acid residues adjacent to the site of peptic hydrolysis in several proteins of known amino-acid sequences. In this communication, a concept is proposed which explains the specificity of pepsin for protein substrates in terms of a hypothetical ‘hydrophobic binding site’.