Cover image for Vol. 17 Issue 14

Editor: Meghan Campbell; Editorial Board Chairs: Thomas Carell, Donald Hilvert, Barbara Imperiali

Online ISSN: 1439-7633

Associated Title(s): ChemCatChem, ChemMedChem, ChemPhysChem, ChemSusChem

8_13/2007Cover Picture: Prediction of the 3D Structure of FMRF-amide Neuropeptides Bound to the Mouse MrgC11 GPCR and Experimental Validation (ChemBioChem 13/2007)

The cover picture shows the predicted structure of the mouse MrgC11 G protein-coupled receptor (GPCR) with the predicted binding site for a signaling tetrapeptide (Phe-(d)Met-Arg-Phe-NH2, a member of the FMRFa family of signal peptides). MrgC11 belongs to the MAS-related gene family and is thought to be involved in pain sensation or modulation. These predictions led to the identification of several residues critical for ligand binding (see inset), while mutagenesis and intracellular-calcium-release experiments confirm the dramatic decrease in activity predicted for the Y110A, D161A, and D179A mutants. This validates the accuracy of these predicted structures, which can now be used for structure-based drug design to find small nonpeptide agonists and antagonists for mMrgC11 and perhaps to identify the endogenous ligand. This also validates the MembStruk methodology used in these predictions, which is equally applicable to all GPCR proteins. Details of the modeling, docking, and experimental verification are in the article by W. A. Goddart III et al. on p. 1527 ff.

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