Pepsinogen crystallization

Is Pepsin a Protein , 87 Activity of Pepsin Bonds Split, 89 Pepsinogen Crystallization and Properties, 89 Pepsinogen in Urine and Blood, 89 Source of Uropepsin, 91... 

Pepsin is secreted as the inactive pepsinogen, which is activated by H+ ions at a pH below 5. Determination of its crystal structure revealed that in the proenzyme the N-terminal 44-residue peptide segment lies across the active site, blocking it.384 At low pH the salt bridges that stabilize the proenzyme are disrupted and the active site is opened up to substrates. 

The first structure of human renin was obtained from prorenin produced by expression of its cDNA in transfected mammalian cells. Prorenin was cleaved in the laboratory to renin using the protease trypsin. Because the carbohydrates in renin are not required for bioactivity, oligosaccharides were removed enzymatically. This process facilitates crystallization in some cases and also removes the contribution of the heterogeneous sugar chains to the diffraction pattern. The structure was determined without the use of heavy-atom derivatives, by application of molecular replacement techniques based on the atomic coordinates of porcine pepsinogen as the model. The molecular dynamic method of refinement was used extensively to arrive at a 2.5 A resolution structure. However, some of the loop regions were not well resolved in this structure (Sielecki et al, 1989 Sail et al, 1990). 

Herriott RM. Isolation, crystallization, and properties of swine pepsinogen. J Gen... 

Pepsin. Pepsin is derived from a z3rmogen, pepsinogen, which occurs in gastric mucosa. Pepsinogen has been obtmned from various animals and crystallized from swine. The various preparations are activated by... 

We also have crystals of chymosin (6), the acid proteinase from Mucor pusillus (7), chicken pepsin (8), and chicken pepsinogen (8), the first two of which are large and very suitable for x-ray analysis. Dr. C. W. Bunn and his co-workers made preliminary x-ray studies of chymosin but the method of isomorphous replacement was unsuccessful, as simple heavy atom derivatives proved impossible to prepare. Both we and Professor B. Foltmann and Dr. S. Larsen of Copenhagen have continued x-ray studies on chymosin, but have also met difficulties. More recently, we have began to use the structural information from the Endothia parastica enzyme to solve the structure of chymosin by using the method of molecular replacement. 

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