5fbe

COMPLEMENT FACTOR D IN COMPLEX WITH COMPOUND2

spinqualitylabelsall models 5fbe, resolution 1.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5fbe is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.43Å Ligands: 5W5, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CFAD_HUMAN Defects in CFD are the cause of complement factor D deficiency (CFDD) [MIM:613912. CFDD is an immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway. Function CFAD_HUMAN Factor D cleaves factor B when the latter is complexed with factor C3b, activating the C3bbb complex, which then becomes the C3 convertase of the alternate pathway. Its function is homologous to that of C1s in the classical pathway. Publication Abstract from PubMed Complement is a key component of the innate immune system, recognizing pathogens and promoting their elimination. Complement component 3 (C3) is the central component of the system. Activation of C3 can be initiated by three distinct routes-the classical, the lectin and the alternative pathways-with the alternative pathway also acting as an amplification loop for the other two pathways. The protease factor D (FD) is essential for this amplification process, which, when dysregulated, predisposes individuals to diverse disorders including age-related macular degeneration and paroxysmal nocturnal hemoglobinuria (PNH). Here we describe the identification of potent and selective small-molecule inhibitors of FD. These inhibitors efficiently block alternative pathway (AP) activation and prevent both C3 deposition onto, and lysis of, PNH erythrocytes. Their oral administration inhibited lipopolysaccharide-induced AP activation in FD-humanized mice. These data demonstrate the feasibility of inhibiting the AP with small-molecule antagonists and support the development of FD inhibitors for the treatment of complement-mediated diseases. Small-molecule factor D inhibitors targeting the alternative complement pathway.,Maibaum J, Liao SM, Vulpetti A, Ostermann N, Randl S, Rudisser S, Lorthiois E, Erbel P, Kinzel B, Kolb FA, Barbieri S, Wagner J, Durand C, Fettis K, Dussauge S, Hughes N, Delgado O, Hommel U, Gould T, Sweeney AM, Gerhartz B, Cumin F, Flohr S, Schubart A, Jaffee B, Harrison R, Risitano AM, Eder J, Anderson K Nat Chem Biol. 2016 Oct 24. doi: 10.1038/nchembio.2208. PMID:27775713 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Complement C3 3D structures Complement factor 3D structures

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