1pca
From Proteopedia
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THREE DIMENSIONAL STRUCTURE OF PORCINE PANCREATIC PROCARBOXYPEPTIDASE A. A COMPARISON OF THE A AND B ZYMOGENS AND THEIR DETERMINANTS FOR INHIBITION AND ACTIVATION
Overview
The three-dimensional structure of procarboxypeptidase A (PCPA) from, porcine pancreas has been determined at 2 A resolution and refined to a, crystallographic R-factor of 0.198, with a root-mean-square deviation from, ideal values for bond lengths of 0.015 A and for angles of 2.1 degrees. It, is compared with procarboxypeptidase B (PCPB) from the same tissue. The, 94/95 residue activation segments of PCPA/PCPB have equivalent folds: an, N-terminal globular region with an open sandwich antiparallel, alpha/antiparallel beta topology, followed by an extended alpha-helical, segment, the connection to the enzyme. Alignment of the secondary, structures of the activation segments of PCPA and PCPB (residues A1 to, A99) indicates a two residue insertion between residues A34 and A35 and a, C-terminal helix that is two turns longer in PCPA compared to PCPB. A, deletion is observed between residues A43 to A45, the region containing, the short 3(10) helix that covers the active site in PCPB. The globular, region (A4 to A80) shields the preformed active center of carboxypeptidase, A (CPA), but none of the residues involved in catalysis makes direct, contacts with the activation segment. In contrast, subsites S2, S3 and S4, of the enzyme, involved in the binding of peptidic substrates, are blocked, by specific contacts with residues AspA36, TrpA38, ArgA47, AspA53 and, GluA86 of the activation segment. It has been described that several, residues of CPA exhibit different conformations in the free enzyme, compared to when substrate is bound: Arg127, Arg145, Glu270 and Tyr248. In, PCPA all of these residues are found in the "active" conformation, as if, substrate were actually bound. The presence of a ligand, tentatively, interpreted as a free amino acid (Val) in the active center could explain, this fact. The connecting region (A80 to A99), the target for proteolytic, activation, establishes fewer contacts with the enzyme in PCPA than in, PCPB. The activation segment of PCPA (A4 to A99) remains bound to the, enzyme after the first trypsin cleavage between ArgA99-Ala1 probably due, to the stability conferred on it by the alpha-helix (alpha 3) of the, connecting segment. These and other structural features may explain the, differences in intrinsic activity and different rates or proteolytic, activation of each zymogen.
About this Structure
1PCA is a Single protein structure of sequence from Sus scrofa with ZN, CIT and VAL as ligands. Active as Carboxypeptidase A, with EC number 3.4.17.1 Full crystallographic information is available from OCA.
Reference
Three-dimensional structure of porcine pancreatic procarboxypeptidase A. A comparison of the A and B zymogens and their determinants for inhibition and activation., Guasch A, Coll M, Aviles FX, Huber R, J Mol Biol. 1992 Mar 5;224(1):141-57. PMID:1548696
Page seeded by OCA on Tue Nov 20 23:40:56 2007
