Crystal structure of bovine procarboxypeptidase A-S6 subunit III, a highly structured truncated zymogen E.
Subunit III, a defective serine endopeptidase lacking the typical N-terminal hydrophobic dipeptide is secreted by the pancreas of ruminant species as part of the bovine ternary complex procarboxypeptidase A-S6. Two monoclinic crystal forms were obtained and subsequently used to solve its X-ray structure. The highest resolution model of subunit III was refined at 1.7 A resolution to a crystallographic R-factor of 18.4%, with r.m.s. bond deviations from ideality of 0.012 A. About 80% of the model presents the characteristic architecture of trypsin-like proteases. The remaining zones, however, have well-defined, unique conformations. The regions from residues 70 to 80 and from 140 to 155 present maximum distances of 16 and 18 A relative to serine proteases and zymogens. Comparisons with the structures of porcine elastase 1 and chymotrypsinogen A indicate that the specific binding pocket of subunit III adopts a zymogen-like conformation and thus provide a basis for its inactivity. In general, the structural analysis of subunit III strongly suggests that it corresponds to a truncated version of a new class of highly structured elastase-like zymogen molecules. Based on the structures of subunit III and elastase 1, it is concluded that large concerted movements are necessary for the activation of zymogen E.
Pignol
D
D
Laboratoire de Cristallographie et de Cristallogénès des Protéines, Institut de Biologie Structurale, Grenoble, France.
Gaboriaud
C
C
Michon
T
T
Kerfelec
B
B
Chapus
C
C
Fontecilla-Camps
J C
JC
D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009038:Motion; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism; D010179:Pancreas / Q000201:enzymology; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism
D004792:Enzyme Precursors; D009097:Multienzyme Complexes; C055863:procarboxypeptidase A-S6; D012697:Serine Endopeptidases; C028734:protease E; C028736:zymogen E