2V77
Crystal Structure of Human Carboxypeptidase A1
Summary for 2V77
Entry DOI | 10.2210/pdb2v77/pdb |
Descriptor | CARBOXYPEPTIDASE A1, OCTANE-1,3,5,7-TETRACARBOXYLIC ACID, ZINC ION, ... (5 entities in total) |
Functional Keywords | metal-binding, metalloprotease, carboxypeptidase, protein degradation, zinc, zymogen, protease, secreted, hydrolase |
Biological source | HOMO SAPIENS (HUMAN) |
Total number of polymer chains | 2 |
Total formula weight | 70835.95 |
Authors | Pallares, I.,Fernandez, D.,Comellas-Bigler, M.,Fernandez-Recio, J.,Ventura, S.,Aviles, F.X.,Vendrell, J. (deposition date: 2007-07-27, release date: 2008-07-01, Last modification date: 2024-10-16) |
Primary citation | Pallares, I.,Fernandez, D.,Comellas-Bigler, M.,Fernandez-Recio, J.,Ventura, S.,Aviles, F.X.,Bode, W.,Vendrell, J. Direct interaction between a human digestive protease and the mucoadhesive poly(acrylic acid). Acta Crystallogr. D Biol. Crystallogr., D64:784-791, 2008 Cited by PubMed Abstract: Carboxypeptidase A1 has been the subject of extensive research in the last 30 y and is one of the most widely studied zinc metalloenzymes. However, the three-dimensional structure of the human form of the enzyme is not yet available. This report describes the three-dimensional structure of human carboxypeptidase A1 (hCPA1) derived from crystals that belong to the tetragonal space group P4(3)2(1)2 and diffract to 1.6 angstroms resolution. A description of the ternary complex hCPA1-Zn2+-poly(acrylic acid) is included as a model of the interaction of mucoadhesive polymers with proteases in the gastrointestinal tract. The direct mode of interaction between poly(acrylic acid) and the active site of the target protease was confirmed by in vitro inhibition assays. The structure was further analyzed in silico through the optimal docking-area method. The characterization of binding sites on the surface of hCPA1 and a comparison with other available carboxypeptidase structures provided further insights into the formation of multiprotein complexes and the activation mechanisms of carboxypeptidase zymogens. The high-resolution structure of hCPA1 provides an excellent template for the modelling of physiologically relevant carboxypeptidases and could also contribute to the design of specific agents for biomedical purposes. PubMed: 18566513DOI: 10.1107/S0907444908013474 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (1.603 Å) |
Structure validation
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