On the functional organization of glutamyl endopeptidases

The paper presents a short survey of the authors' and literature data. Anal ysis of known primary and tertiary structures of glutamyl endopeptidases ha s revealed their structural similarity with the chymotrypsin group and allo wed identification of a number of important amino acid residues, in particu lar, of those forming the active site and the substrate-binding pocket. Glu tamyl endopeptidases appear to constitute a separate evolutionary branch of chymotrypsin-like enzymes, marked by cardinally changed specificity. Resid ue arrangement in the catalytic triad and in the oxyanion hole is typical o f the active sites of serine proteinases. The structures of the substrate-b inding region in glutamyl endopeptidases and bacterial trypsin and chymotry psin are also similar in general, differing only in the nature of the key r esidues. However, although the structure of the substrate-binding pocket in glutamyl endopeptidases has been known, the molecular mechanism underlying its specificity for the amino acid residues with negatively charged side c hains will remain unclear until one knows how the negative charge of the su bstrate is compensated. The available data suggest that the pKa of an imida zole group in glutamyl endopeptidases is substantially shifted by some mean s. The probable mechanisms of autocatalytic excision of prosequences in glu tamyl endopeptidases are also discussed.