6d26 | pdb_00006d26

Crystal structure of the prostaglandin D2 receptor CRTH2 with fevipiprant

spinqualitylabelsall models 6d26, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6d26 is a 1 chain structure with sequence from Escherichia virus T4 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.798Å Ligands: FSY, OLA, PGE, PGO, SIN, SO4, YCM Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer. PD2R2_HUMAN Receptor for prostaglandin D2 (PGD2). Coupled to the G(i)-protein. Receptor activation may result in pertussis toxin-sensitive decreases in cAMP levels and Ca(2+) mobilization. PI3K signaling is also implicated in mediating PTGDR2 effects. PGD2 induced receptor internalization. CRTH2 internalization can be regulated by diverse kinases such as, PKC, PKA, GRK2, GPRK5/GRK5 and GRK6. Receptor activation is responsible, at least in part, in immune regulation and allergic/inflammation responses. Publication Abstract from PubMed The signaling of prostaglandin D2 (PGD2) through G-protein-coupled receptor (GPCR) CRTH2 is a major pathway in type 2 inflammation. Compelling evidence suggests the therapeutic benefits of blocking CRTH2 signaling in many inflammatory disorders. Currently, a number of CRTH2 antagonists are under clinical investigation, and one compound, fevipiprant, has advanced to phase 3 clinical trials for asthma. Here, we present the crystal structures of human CRTH2 with two antagonists, fevipiprant and CAY10471. The structures, together with docking and ligand-binding data, reveal a semi-occluded pocket covered by a well-structured amino terminus and different binding modes of chemically diverse CRTH2 antagonists. Structural analysis suggests a ligand entry port and a binding process that is facilitated by opposite charge attraction for PGD2, which differs significantly from the binding pose and binding environment of lysophospholipids and endocannabinoids, revealing a new mechanism for lipid recognition by GPCRs. Structures of the Human PGD2 Receptor CRTH2 Reveal Novel Mechanisms for Ligand Recognition.,Wang L, Yao D, Deepak RNVK, Liu H, Xiao Q, Fan H, Gong W, Wei Z, Zhang C Mol Cell. 2018 Oct 4;72(1):48-59.e4. doi: 10.1016/j.molcel.2018.08.009. Epub 2018, Sep 13. PMID:30220562 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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