Pancreatic procarboxypeptidases: their activation processes related to the structural features of the zymogens and activation segments.
The molecular events leading to the complete activation of pancreatic procarboxypeptidases A and B have been investigated. For both proteins the activation process follows a similar general scheme: trypsin is responsible for the first cleavage that separates the active enzyme from the activation segment, the degradation of the activation segment proceeds only from its C-terminal end, and activity release can be correlated with the disappearance of the long forms of the activation segment. In both systems, trypsin and the released carboxypeptidase participate in the trimming of the severed activation regions. However, the rate of enzymatic activation is much faster in the case of procarboxypeptidase B. This phenomenon may be explained by some structural differences in the connecting region which acts as a linker between the globular domain of the activation segment and the N-terminal end of carboxypeptidases and also by the higher efficiency of carboxypeptidase B for the digestion of its own activation segment. It is not due to unfolding of the activation domain, since the isolated activation domain retains its globular conformation in solution.
Vendrell
J
J
Departament de Bioquímica i Biologia Molecular, Universitat Autónoma de Barcelona, Bellaterra.
Guasch
A
A
Coll
M
M
Villegas
V
V
Billeter
M
M
Wider
G
G
Huber
R
R
Wüthrich
K
K
Avilés
F X
FX
D000595:Amino Acid Sequence; D000818:Animals; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000378:metabolism*; D043422:Carboxypeptidases A; D002851:Chromatography, High Pressure Liquid; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010179:Pancreas / Q000201:enzymology*; D011487:Protein Conformation; D051381:Rats; D014357:Trypsin / Q000378:metabolism; D014961:X-Ray Diffraction
D004792:Enzyme Precursors; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D043424:Carboxypeptidase B; D014357:Trypsin