1kwm
From Proteopedia
|
Human procarboxypeptidase B: Three-dimensional structure and implications for thrombin-activatable fibrinolysis inhibitor (TAFI)
Overview
Besides their classical role in alimentary protein degradation, zinc-dependant carboxypeptidases also participate in more selective, regulatory processes like prohormone and neuropeptide processing or, fibrinolysis inhibition in blood plasma. Human pancreatic, procarboxypeptidase B (PCPB) is the prototype for those human, exopeptidases that cleave off basic C-terminal residues and are secreted, as inactive zymogens. One such protein is thrombin-activatable, fibrinolysis inhibitor (TAFI), also known as plasma PCPB, which circulates, in human plasma as a zymogen bound to plasminogen. The structure of human, pancreatic PCPB displays a 95-residue pro-segment consisting of a globular, region with an open-sandwich antiparallel-alpha antiparallel-beta topology, and a C-terminal alpha-helix, which connects to the enzyme moiety. The, latter is a 309-amino acid residue catalytic domain with alpha/beta, hydrolase topology and a preformed active site, which is shielded by the, globular domain of the pro-segment. The fold of the proenzyme is similar, to previously reported procarboxypeptidase structures, also in that the, most variable region is the connecting segment that links both globular, moieties. However, the empty active site of human procarboxypeptidase B, has two alternate conformations in one of the zinc-binding residues, which, account for subtle differences in some of the key residues for substrate, binding. The reported crystal structure, refined with data to 1.6A, resolution, permits in the absence of an experimental structure, accurate, homology modelling of TAFI, which may help to explain its properties.
About this Structure
1KWM is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Carboxypeptidase B, with EC number 3.4.17.2 Full crystallographic information is available from OCA.
Reference
Human procarboxypeptidase B: three-dimensional structure and implications for thrombin-activatable fibrinolysis inhibitor (TAFI)., Barbosa Pereira PJ, Segura-Martin S, Oliva B, Ferrer-Orta C, Aviles FX, Coll M, Gomis-Ruth FX, Vendrell J, J Mol Biol. 2002 Aug 16;321(3):537-47. PMID:12162965
Page seeded by OCA on Fri Feb 15 16:15:29 2008
