journal.pone.0016811.PDF 883,86KB
1000 Titel
  • Chemogenomic Analysis of G-Protein Coupled Receptors and Their Ligands Deciphers Locks and Keys Governing Diverse Aspects of Signalling
1000 Autor/in
  1. Wichard, Jörg D. |
  2. ter Laak, Antonius |
  3. Krause, Gerd |
  4. Heinrich, Nikolaus |
  5. Kühne, Ronald |
  6. Kleinau, Gunnar |
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2011-02-04
1000 Erschienen in
1000 Quellenangabe
  • 6(2): e16811
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2011
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Ergänzendes Material
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Understanding the molecular mechanism of signalling in the important super-family of G-protein-coupled receptors (GPCRs) is causally related to questions of how and where these receptors can be activated or inhibited. In this context, it is of great interest to unravel the common molecular features of GPCRs as well as those related to an active or inactive state or to subtype specific G-protein coupling. In our underlying chemogenomics study, we analyse for the first time the statistical link between the properties of G-protein-coupled receptors and GPCR ligands. The technique of mutual information (MI) is able to reveal statistical inter-dependence between variations in amino acid residues on the one hand and variations in ligand molecular descriptors on the other. Although this MI analysis uses novel information that differs from the results of known site-directed mutagenesis studies or published GPCR crystal structures, the method is capable of identifying the well-known common ligand binding region of GPCRs between the upper part of the seven transmembrane helices and the second extracellular loop. The analysis shows amino acid positions that are sensitive to either stimulating (agonistic) or inhibitory (antagonistic) ligand effects or both. It appears that amino acid positions for antagonistic and agonistic effects are both concentrated around the extracellular region, but selective agonistic effects are cumulated between transmembrane helices (TMHs) 2, 3, and ECL2, while selective residues for antagonistic effects are located at the top of helices 5 and 6. Above all, the MI analysis provides detailed indications about amino acids located in the transmembrane region of these receptors that determine G-protein signalling pathway preferences.
1000 Sacherschließung
lokal Multiple alignment calculation
lokal Sequence databases
lokal Transmembrane receptors
lokal Crystal structure
lokal G-protein signaling
lokal G protein coupled receptors
lokal Sequence alignment
lokal Amino acid analysis
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
1000 Label
1000 Förderer
  1. Bayer-Schering Pharma, Berlin, Germany |
1000 Fördernummer
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1000 Förderprogramm
  1. -
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Bayer-Schering Pharma, Berlin, Germany |
    1000 Förderprogramm -
    1000 Fördernummer -
1000 Objektart article
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