5dhh

The crystal structure of nociceptin/orphanin FQ peptide receptor (NOP) in complex with SB-612111 (PSI Community Target)

spinqualitylabelsall models 5dhh, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dhh is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DGW, OLA, OLC Related: 4ea3 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Publication Abstract from PubMed Understanding the mechanism by which ligands affect receptor conformational equilibria is key in accelerating membrane protein structural biology. In the case of G protein-coupled receptors (GPCRs), we currently pursue a brute-force approach for identifying ligands that stabilize receptors and facilitate crystallogenesis. The nociceptin/orphanin FQ peptide receptor (NOP) is a member of the opioid receptor subfamily of GPCRs for which many structurally diverse ligands are available for screening. We observed that antagonist potency is correlated with a ligand's ability to induce receptor stability (Tm) and crystallogenesis. Using this screening strategy, we solved two structures of NOP in complex with top candidate ligands SB-612111 and C-35. Docking studies indicate that while potent, stabilizing antagonists strongly favor a single binding orientation, less potent ligands can adopt multiple binding modes, contributing to their low Tm values. These results suggest a mechanism for ligand-aided crystallogenesis whereby potent antagonists stabilize a single ligand-receptor conformational pair. The Importance of Ligand-Receptor Conformational Pairs in Stabilization: Spotlight on the N/OFQ G Protein-Coupled Receptor.,Miller RL, Thompson AA, Trapella C, Guerrini R, Malfacini D, Patel N, Han GW, Cherezov V, Calo G, Katritch V, Stevens RC Structure. 2015 Oct 24. pii: S0969-2126(15)00407-4. doi:, 10.1016/j.str.2015.07.024. PMID:26526853 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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