2v77

Publication Abstract from PubMed

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.

Direct interaction between a human digestive protease and the mucoadhesive poly(acrylic acid).,Pallares I, Fernandez D, Comellas-Bigler M, Fernandez-Recio J, Ventura S, Aviles FX, Bode W, Vendrell J Acta Crystallogr D Biol Crystallogr. 2008 Jul;D64(Pt 7):784-91. Epub 2008, Jun 18. PMID:18566513^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.