Web of Science: 13 citas, Scopus: 14 citas, Google Scholar: citas
Direct interaction between a human digestive protease and the mucoadhesive poly(acrylic acid)
Pallarès i Goitiz, Irantzu (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Fernández Fleischhauer, Daniel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Comellas-Bigler, Mireia (Max-Planck Institute of Biochemistry. Proteinase Research Group)
Fernández-Recio, Juan (Barcelona Supercomputing Center)
Ventura, Salvador (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Avilés, Francesc X. (Francesc Xavier) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Bode, Wolfram (Max-Planck Institute of Biochemistry. Proteinase Research Group)
Vendrell i Roca, Josep (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Fecha: 2008
Resumen: 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 P43212 and diffract to 1. 6 Å 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.
Ayudas: European Commission 018830
Ministerio de Educación y Ciencia BIO2004-05879
Ministerio de Educación y Ciencia BIO2005-06753
Ministerio de Educación y Ciencia BIO2007-68046
Agència de Gestió d'Ajuts Universitaris i de Recerca 2005/SGR-1037
Derechos: Tots els drets reservats.
Lengua: Anglès
Documento: Article ; Versió publicada
Materia: Cristal·lografia ; Crystallography ; Carboxypeptidase A1 ; Mucoadhesive polymers ; Zinc metalloenzymes ; Digestive proteases
Publicado en: Acta crystallographica. Section D, Biological crystallography, Vol. 64, Issue 7 (July 2008) , p. 784-791, ISSN 1399-0047

DOI: 10.1107/S0907444908013474


8 p, 1.0 MB

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