Web of Science: 7 citas, Scopus: 7 citas, Google Scholar: citas,
Crystal Structure of Two Anti-Porphyrin Antibodies with Peroxidase Activity
Muñoz Robles, Victor (Universitat Autònoma de Barcelona. Departament de Química)
Maréchal, Jean-Didier (Universitat Autònoma de Barcelona. Departament de Química)
Bahloul, Amel (Centre national de la recherche scientifique (França). Laboratoire d'Enzymologie et Biochimie structurales)
Golinelli-Pimpaneau, Béatrice (Centre national de la recherche scientifique (França). Laboratoire d'Enzymologie et Biochimie structurales)
Sari, Marie-Agnès (Centre national de la recherche scientifique (França). Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques)
Mahy, Jean-Pierre (Centre national de la recherche scientifique (França). Institut de Chimie Moléculaire et des Matériaux d'Orsay)

Fecha: 2012
Resumen: We report the crystal structures at 2. 05 and 2. 45 Å resolution of two antibodies, 13G10 and 14H7, directed against an iron(III)-αααβ-carboxyphenylporphyrin, which display some peroxidase activity. Although these two antibodies differ by only one amino acid in their variable λ-light chain and display 86% sequence identity in their variable heavy chain, their complementary determining regions (CDR) CDRH1 and CDRH3 adopt very different conformations. The presence of Met or Leu residues at positions preceding residue H101 in CDRH3 in 13G10 and 14H7, respectively, yields to shallow combining sites pockets with different shapes that are mainly hydrophobic. The hapten and other carboxyphenyl-derivatized iron(III)-porphyrins have been modeled in the active sites of both antibodies using protein ligand docking with the program GOLD. The hapten is maintained in the antibody pockets of 13G10 and 14H7 by a strong network of hydrogen bonds with two or three carboxylates of the carboxyphenyl substituents of the porphyrin, respectively, as well as numerous stacking and van der Waals interactions with the very hydrophobic CDRH3. However, no amino acid residue was found to chelate the iron. Modeling also allows us to rationalize the recognition of alternative porphyrinic cofactors by the 13G10 and 14H7 antibodies and the effect of imidazole binding on the peroxidase activity of the 13G10/porphyrin complexes.
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Lengua: Anglès.
Documento: article ; recerca ; publishedVersion
Materia: Porphyrins ; Peroxidases ; Cofactors (biochemistry) ; Imidazole ; Haptens ; Iron ; Crystal structure ; Enzyme-linked immunoassays
Publicado en: PLoS one, Vol. 7 Issue 12 (December 2012) , p. e51128, ISSN 1932-6203

DOI: 10.1371/journal.pone.0051128
PMID: 23240001

18 p, 4.1 MB

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