RT Journal Article SR Electronic T1 A Molecular Pharmacologist's Guide to GPCR Crystallography JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP mol.115.099663 DO 10.1124/mol.115.099663 A1 Chayne L. Piscitelli A1 James Kean A1 Chris de Graaf A1 Xavier Deupi YR 2015 UL http://molpharm.aspetjournals.org/content/early/2015/07/07/mol.115.099663.abstract AB G protein-coupled receptor (GPCR) structural biology has progressed dramatically in the last decade. There are now over 120 GPCR crystal structures deposited in the Protein Data Bank of 32 different receptors from families scattered across the phylogenetic tree, including Class B, C, and Frizzled GPCRs. These structures have been obtained in combination with a wide variety of ligands, and captured in a range of conformational states. This surge in structural knowledge has enlightened research into the molecular recognition of biologically active molecules, the mechanisms of receptor activation, the dynamics of functional selectivity, and fuelled structure- based drug design efforts for GPCRs. Here we summarize the innovations in both protein engineering/molecular biology and crystallography techniques that have led to these advances in GPCR structural biology, and discuss how they may influence the resulting structural models. We also provide a brief molecular pharmacologist's guide to GPCR X-ray crystallography, outlining some key aspects in the process of structure determination, with the goal to encourage non-crystallographers to interrogate structures at the molecular level. Finally we show how chemogenomics approaches can be used to marry the wealth of existing receptor pharmacology data with the expanding repertoire of structures, providing a deeper understanding of the mechanistic details of GPCR function.