1nsa
THREE-DIMENSIONAL STRUCTURE OF PORCINE PROCARBOXYPEPTIDASE B: A STRUCTURAL BASIS OF ITS INACTIVITY
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OverviewOverview
Procarboxypeptidase B is converted to enzymatically active, carboxypeptidase B by limited proteolysis catalysed by trypsin, removing, the long N-terminal activation segment of 95 amino acids. The, three-dimensional crystal structure of procarboxypeptidase B from porcine, pancreas has been determined at 2.3 A resolution and refined to a, crystallographic R-factor of 0.169. The functional determinants of its, enzymatic inactivity and of its activation by limited proteolysis have, thus been unveiled. The activation segment folds in a globular region with, an open sandwich antiparallel-alpha antiparallel-beta topology and in a C, terminal alpha-helix which connects it to the enzyme moiety. The globular, region (A7-A82) shields the preformed active site, and establishes, specific interactions with residues important for substrate recognition., AspA41 forms a salt bridge with Arg145, which in active carboxypeptidase, binds the C-terminal carboxyl group of substrate molecules. The connecting, region occupies the putative extended substrate binding site. The scissile, peptide bond cleaved by trypsin during activation is very exposed. Its, cleavage leads to the release of the activation segment and to exposure of, the substrate binding site. An open-sandwich folding has been observed in, a number of other proteins and protein domains. One of them is the, C-terminal fragment of L7/L12, a ribosomal protein from Escherichia coli, that displays a topology similar to the activation domain of, procarboxypeptidase.
About this StructureAbout this Structure
1NSA is a Single protein structure of sequence from Sus scrofa with ZN and BEN as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Three-dimensional structure of porcine procarboxypeptidase B: a structural basis of its inactivity., Coll M, Guasch A, Aviles FX, Huber R, EMBO J. 1991 Jan;10(1):1-9. PMID:1989878
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