6c1q

Crystal structure of human C5a receptor in complex with an orthosteric antagonist PMX53 and an allosteric antagonist NDT9513727

spinqualitylabelsall models 6c1q, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6c1q is a 2 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 9P2 NonStd Res: ACE, ORN, YCM, ZAL Gene: C5AR1, C5AR, C5R1 ("Bacillus coli" Migula 1895) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [C562_ECOLX] Electron-transport protein of unknown function. Publication Abstract from PubMed The C5a receptor (C5aR) is a G-protein-coupled receptor (GPCR) that can induce strong inflammatory response to the anaphylatoxin C5a. Targeting C5aR has emerged as a novel anti-inflammatory therapeutic method. However, developing potent C5aR antagonists as drugs has proven difficult. Here, we report two crystal structures of human C5aR in ternary complexes with the peptide antagonist PMX53 and a non-peptide antagonist, either avacopan or NDT9513727. The structures, together with other biophysical, computational docking and cell-based signaling data, reveal the orthosteric action of PMX53 and its effect of stabilizing the C5aR structure, as well as the allosteric action of chemically diverse non-peptide C5aR antagonists with different binding poses. Structural comparison analysis suggests the presence of similar allosteric sites in other GPCRs. We also discuss critical structural features of C5aR in activation, including a novel conformation of helix 8. On the basis of our results, we suggest novel strategies for developing C5aR-targeting drugs. Orthosteric and allosteric action of the C5a receptor antagonists.,Liu H, Kim HR, Deepak RNVK, Wang L, Chung KY, Fan H, Wei Z, Zhang C Nat Struct Mol Biol. 2018 Jun;25(6):472-481. doi: 10.1038/s41594-018-0067-z. Epub, 2018 Jun 4. PMID:29867214 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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