In silico approaches towards the understanding of the structure-function relationships in metabotropic glutamate receptors (mGluRs) and other family C GPRCs.
Family C of the superfamily of G-protein coupled receptors is a growing family of heptahelical receptors, which includes, among others, metabotropic glutamate receptors (mGluRs) and GABA(B) receptors. A common feature of all the members of family C is a structural architecture much more complex than any other GPCRs. Computational studies, including homology modeling, pharmacophore definitions and molecular dynamics simulations have constantly flanked experimental approaches in the understanding of the receptor functioning. The present review will discuss the evolution of our perception in family C GPCRs structure and function as emerged from the critical comparison of in silico methods with molecular biology and crystallographic experiments.
Costantino
Gabriele
G
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, Italy. gabri@unipg.it
D000494:Allosteric Regulation; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008024:Ligands; D008958:Models, Molecular; D016296:Mutagenesis; D033902:Periplasmic Binding Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018080:Receptors, GABA-B / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship
D008024:Ligands; D033902:Periplasmic Binding Proteins; D043562:Receptors, G-Protein-Coupled; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate