6qzh

Structure of the human CC Chemokine Receptor 7 in complex with the intracellular allosteric antagonist Cmp2105 and the insertion protein Sialidase NanA

spinqualitylabelsall models 6qzh, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qzh is a 1 chain structure with sequence from Homo sapiens and Streptococcus pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: JLW, NA, PGE, TAR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function NANA_STRR6 CCR7_HUMAN Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions. Publication Abstract from PubMed The CC chemokine receptor 7 (CCR7) balances immunity and tolerance by homeostatic trafficking of immune cells. In cancer, CCR7-mediated trafficking leads to lymph node metastasis, suggesting the receptor as a promising therapeutic target. Here, we present the crystal structure of human CCR7 fused to the protein Sialidase NanA by using data up to 2.1 A resolution. The structure shows the ligand Cmp2105 bound to an intracellular allosteric binding pocket. A sulfonamide group, characteristic for various chemokine receptor ligands, binds to a patch of conserved residues in the Gi protein binding region between transmembrane helix 7 and helix 8. We demonstrate how structural data can be used in combination with a compound repository and automated thermal stability screening to identify and modulate allosteric chemokine receptor antagonists. We detect both novel (CS-1 and CS-2) and clinically relevant (CXCR1-CXCR2 phase-II antagonist Navarixin) CCR7 modulators with implications for multi-target strategies against cancer. Structural Basis for Allosteric Ligand Recognition in the Human CC Chemokine Receptor 7.,Jaeger K, Bruenle S, Weinert T, Guba W, Muehle J, Miyazaki T, Weber M, Furrer A, Haenggi N, Tetaz T, Huang CY, Mattle D, Vonach JM, Gast A, Kuglstatter A, Rudolph MG, Nogly P, Benz J, Dawson RJP, Standfuss J Cell. 2019 Aug 22;178(5):1222-1230.e10. doi: 10.1016/j.cell.2019.07.028. PMID:31442409 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also CXC chemokine receptor

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