| Literature DB >> 15282370 |
Riccardo Bertini1, Marcello Allegretti, Cinzia Bizzarri, Alessio Moriconi, Massimo Locati, Giuseppe Zampella, Maria N Cervellera, Vito Di Cioccio, Maria C Cesta, Emanuela Galliera, Fernando O Martinez, Rosa Di Bitondo, Giulia Troiani, Vilma Sabbatini, Gaetano D'Anniballe, Roberto Anacardio, Juan C Cutrin, Barbara Cavalieri, Fabrizio Mainiero, Raffaele Strippoli, Pia Villa, Maria Di Girolamo, Franck Martin, Marco Gentile, Angela Santoni, Daniela Corda, Giuseppe Poli, Alberto Mantovani, Pietro Ghezzi, Francesco Colotta.
Abstract
The chemokine CXC ligand 8 (CXCL8)/IL-8 and related agonists recruit and activate polymorphonuclear cells by binding the CXC chemokine receptor 1 (CXCR1) and CXCR2. Here we characterize the unique mode of action of a small-molecule inhibitor (Repertaxin) of CXCR1 and CXCR2. Structural and biochemical data are consistent with a noncompetitive allosteric mode of interaction between CXCR1 and Repertaxin, which, by locking CXCR1 in an inactive conformation, prevents signaling. Repertaxin is an effective inhibitor of polymorphonuclear cell recruitment in vivo and protects organs against reperfusion injury. Targeting the Repertaxin interaction site of CXCR1 represents a general strategy to modulate the activity of chemoattractant receptors.Entities:
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Year: 2004 PMID： 15282370 PMCID： PMC511013 DOI： 10.1073/pnas.0402090101
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205