Trypsinogen structure

Fehlhammer, H., Bode, W., Huber, R. Crystal structure of bovine trypsinogen at 1.8 A resolution. 11. Crystallographic refinement, refined crystal structure and comparison with bovine trypsin. J. Mol. Biol. 

Huber and associates have refined the structure of trypsinogen in methanol-water, inidally at 213 K (Singh et al., 1980) and subsequently... 

In trypsinogen, a region of the protein at the binding pocket is disordered, indicating conformational flexibility.133,134 On activation or on the addition of a small peptide that can bind to the buried Asp-194, this region takes on a well-defined structure. 

The inactive precursors are called trypsinogen, pepsinogen, chymotrypsino-gen, and procarboxypeptidase. These precursors are converted to the active enzymes by hydrolytic cleavage of a few specific peptide bonds under the influence of other enzymes (trypsin, for example, converts chymotrypsinogen to chymotrypsin). The digestive enzymes do not appear to self-destruct, probably because they are so constructed that it is sterically impossible to fit a part of one enzyme molecule into the active site of another. In this connection, it is significant that chymotrypsin attacks denatured proteins more rapidly than natural proteins with their compact structures of precisely folded chains. 

In conclusion, the double mutant pepsin T77D/G78(S)S79 was also able to activate bovine trypsinogen to trypsin by the selective cleavage of the Lys6-Ile7 bond of trypsinogen. Results of this study suggest that the structure of the active site flap contribute to the Si substrate specificity for basic amino acid residues in aspartic proteinases. 

It is evident that monochromatic rotations are a useful adjunct to any study of protein structure, but a final illustration of the insight that rotatory dispersion can provide may be seen in the conformational analysis of ehy-motrypsinogen activation. Neurath et al. (1956) have found an exact correlation between the rate of activation of both chymotrypsinogen and trypsinogen as measured by the enzymatic activity of their products and the rate at which their specific rotations become more positive, a change which Neurath and Dixon (1957) suggest represents an increase in helical content. By dispersion measurements on chymotrypsinogen and x-chymo-trypsin, Imahori et al. (1960) have demonstrated that a twofold increase in helical content, from 12 to 24 %, indeed occurs. They are thus able to esti-... 

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