Modelling of the membrane receptor CXCR3 and its complexes with CXCL9, CXCL10 and CXCL11 chemokines: putative target for new drug design.
Mol Immunol
; 47(2-3): 332-9, 2009 Dec.
Article
en En
| MEDLINE
| ID: mdl-19800124
ABSTRACT
The chemokines play a key role in immune and inflammatory responses by promoting recruitment and activation of different subpopulations of leukocytes. These comprise over 50 proteins grouped into four classes, in basis to the arrangement of conserved cysteine residues within the sequence. CXCL9, CXCL10 and CXCL11 are the members of the family of ELR-CXC chemokines and bind the same CXCR3 receptor. During the past few years, several studies have demonstrated a pathogenetic role of CXCR3 and its ligands in many human inflammatory diseases. The blockade of CXCR3 interactions with its ligands has been suggested as a possible therapeutic target for the treatment of these diseases. Therefore, we modelled the three-dimensional structure of CXCL9 and CXCR3, and, successively, of the CXCL9/CXCR3 complex in comparison to CXCL10/CXCR3 and CXCL11/CXCR3 complexes. We have then shown the structural determinants of these interactions and their physico-chemical features. Finally, the interaction residues involved in the formation of the complexes have been highlighted and analyzed in order to be used for drug design.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diseño de Fármacos
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Modelos Moleculares
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Membrana Celular
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Quimiocina CXCL9
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Quimiocina CXCL10
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Quimiocina CXCL11
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Receptores CXCR3
Límite:
Animals
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Humans
Idioma:
En
Revista:
Mol Immunol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Italia