Three different forms of tryptophanyl‐tRNA synthetase can be isolated from pancreatic extracts. Structural, immunological and catalytic properties of these various forms have been compared. The native enzyme is a dimeric molecule of molecular weight 108000. Two other forms, of molecular weight 85000 and 82000, are composed of two polypeptide chains identical with the carboxyl terminal region of the native subunits. These molecules are supposed to derive from the original protein by removal, from the amino‐terminal part of each subunit, of a fragment of 11000 to 13000 molecular weight. Such removal modifies the shape and the stability of the molecule and decreases its specific activity. The origin of the derived forms is attributed to proteolysis. In fact, limited proteolysis of purified tryptophanyl‐tRNA synthetase, in its native form, by elastase, results in the formation of an active compound, similar to one of the tryptophanyl‐tRNA synthetase derived forms. Furthermore, incubation with “elastolytic fractions” prepared from pancreatic extracts presenting a particularly high level of proteolytic activity produces the same cleavage in tryptophanyl‐tRNA synthetase polypeptide chain.

Treatment of purified tryptophanyl‐tRNA synthetase with either chymotrypsin, papain, subtilisin or elastase converts all the enzyme into a high‐molecular‐weight intermediate. This protease‐resistant core molecule has the same dimeric structure as the native protein and possesses the ability to bind substrates (tryptophan, ATP and tRNATrp) but is catalytically inactive. The monomer molecular weight of the protease‐treated enzyme is 39000 compared to 54000 for the intact molecule. Chemical studies indicate that proteases excise the amino‐terminal part of the polypeptide chain. It has been demonstrated previously that removal of a 13000‐dalton fragment from the amino‐terminal region of the tryptophanyl‐tRNA synthetase converts the native enzyme to another active form. Cleavage of 20 additional amino acids produces the inactive protease‐resistant core.

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