The inactive subunit of ruminant procarboxypeptidase A-S6 complexes. Structural basis of inactivity and physiological role.
Subunit III has so far been found only in the pancreas of ruminants in a non-covalent association (procarboxypeptidase A-S6) with two different proteins: the procarboxypeptidase A itself (subunit I) and a C-type chymotrypsinogen (subunit II). In contrast with these latter two proteins, which are zymogens of pancreatic proteases, subunit III seems to be devoid of any activity towards specific substrates of pancreatic proteases. However, it possesses a weakly functional active site which allows it to hydrolyze a non-specific ester, p-nitrophenyl acetate, and to react with several active-site titrants. The binding of proflavin to subunit III shows that this protein owns a non-polar binding site with a very high Kd compared to that of chymotrypsin. The comparison of the amino acid sequences of subunit III and some serine proteases showed that subunit III is closely related to an elastase. Models of the tertiary structure of subunit III suggest a conformational modification that affects the substrate binding and could explain the lack of specific enzymatic activity. The presence of subunit III in the ternary complex is not related to an enzymatic function. This protein does not participate in the activation process of subunit I but prevents the denaturation of this subunit at low pH. This may represent its biological role in the acidic environment of the duodenum in ruminants.
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002268:Carboxypeptidases / Q000378:metabolism*; D043422:Carboxypeptidases A; D002417:Cattle; D004792:Enzyme Precursors / Q000378:metabolism*; D004950:Esterases / Q000378:metabolism; D006041:Goats; D006863:Hydrogen-Ion Concentration; D009596:Nitrophenols / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase; D011370:Proflavine / Q000378:metabolism; D011487:Protein Conformation; D012756:Sheep; D014357:Trypsin / Q000378:metabolism
D004792:Enzyme Precursors; D009596:Nitrophenols; C008642:4-nitrophenyl acetate; D011370:Proflavine; D004950:Esterases; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D010196:Pancreatic Elastase; D014357:Trypsin