1zg7

Crystal Structure of 2-(5-{[amino(imino)methyl]amino}-2-chlorophenyl)-3-sulfanylpropanoic acid Bound to Activated Porcine Pancreatic Carboxypeptidase BCrystal Structure of 2-(5-{[amino(imino)methyl]amino}-2-chlorophenyl)-3-sulfanylpropanoic acid Bound to Activated Porcine Pancreatic Carboxypeptidase B

Structural highlights 1zg7 is a 3 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.75Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CBPB1_PIG Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed This paper presents the crystal structure of porcine pancreatic carboxypeptidase B (pp-CpB) in complex with a variety of thiol-based inhibitors that were developed as antagonists of activated thrombin-activatable fibrinolysis inhibitor (TAFIa). Recent studies have indicated that a selective inhibitor of TAFIa could enhance the efficacy of existing thrombolytic agents for the treatment of acute myocardial infarction, one of the most prevalent forms of heart attacks. Unfortunately, activated TAFIa rapidly degrades in solution and cannot be used for crystallographic studies. In contrast, porcine pancreatic CpB is stable at room temperature and is available from commercial sources. Both pancreatic CpB and TAFIa are zinc-based exopeptidases, and the proteins share a 47% sequence identity. The homology improves considerably in the active site where nearly all of the residues are conserved. The inhibitors used in this study were designed to mimic a C-terminal arginine residue, one of the natural substrates of TAFIa. The X-ray structures show that the thiol group chelates the active site zinc, the carboxylic acid forms a salt bridge to Arg145, and the guanidine group forms two hydrogen bonds to Asp255. A meta-substituted phenyl was introduced into our inhibitors to reduce conformational freedom. This modification vastly improved the selectivity of compounds against other exopeptidases that cleave basic residues. Comparisons between structures indicate that selectivity derives from the interaction between the guanidine group in the inhibitors and an acidic active site residue. The location of this acidic residue is not conserved in the various carboxypeptidases. Crystal structures of potent thiol-based inhibitors bound to carboxypeptidase B.,Adler M, Bryant J, Buckman B, Islam I, Larsen B, Finster S, Kent L, May K, Mohan R, Yuan S, Whitlow M Biochemistry. 2005 Jul 5;44(26):9339-47. PMID:15982000 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Carboxypeptidase 3D structures

spinqualitylabelsall models 1zg7, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image