The three-dimensional structure of human procarboxypeptidase A2. Deciphering the basis of the inhibition, activation and intrinsic activity of the zymogen

摘要: The three-dimensional structure of human procarboxypeptidase A2 has been determined using X-ray crystallography at 1.8 A resolution. This is the first detailed structural report a pancreatic carboxypeptidase and its zymogen. Human formed by pro-segment 96 residues, which inhibits enzyme, moiety 305 residues. pro-enzyme maintains general fold when compared with other non-human counterparts. globular part docks into enzyme shields S2-S4 substrate binding sites, promoting inhibition. Interestingly, important differences are found in allow identification determinants diverse activation behaviours procarboxypeptidases A1, B A2, particularly latter. benzylsuccinic inhibitor able to diffuse active site crystals. zymogen-inhibitor complex solved 2.2 enters through channel interface between regions interacts elements site. derived features explain intrinsic activity A1/A2 pro-enzymes for small substrates.