Structural biology

Structural biology

GPCR structures are invaluable for receptor function studies and for rational drug design. Technological advances in X-ray crystallography and cryogenic electron microscopy (cryo-EM) have led to an explosion of structures covering all major GPCR classes and diverse ligands (see latest statistics). However, there are still no structures for the vast majority of the 398 non-olfactory GPCRs and technological limitations remain that restrict which ligand complexes can be attained.

In the last years, the Gloriam group has set up GPCR crystallography and cryo-EM in collaboration with structural biology professors Jette S. Kastrup and Michael Gajhede. The projects aim to cover more receptors and ligands, including in-house medicinal chemistry targets and biased ligands. We are part of a structural biology network, ISBUC at the University of Copenhagen. We collect data at the new state-of-the-art synchrotron MAX IV in Lund (X-ray crystallography), two national cryo-EM core facilities and a number of international resources.

The Gloriam group also maintain an online resource for GPCR structure determination based on all published structures. The major features include design of new receptor constructs and browsing of experimental methods and reagents (Structure Constructs section in https://gpcrdb.org). The GPCRdb database also features a number of tools to analyse existing structures and, where lacking, structure models for nearly all GPCRs in the inactive, active and intermediate states.