5hcd

Ternary complex of human Complement C5 with Ornithodoros moubata OmCI and Rhipicephalus microplus RaCI2

spinqualitylabelsall models 5hcd, resolution 2.98Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5hcd is a 4 chain structure with sequence from Homo sapiens, Ornithodoros moubata and Rhipicephalus microplus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.98Å Ligands: CYS, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C5I2_RHIMP Complement inhibitor (PubMed:27018802). Prevents complement-mediated C5 activation by binding to C5 (PubMed:27018802). Binds C5 at a different binding site than the other tick complement inhibitors OmCI and CirpT1, and the drug eculizumab (By similarity).[UniProtKB:A0A146B485] Publication Abstract from PubMed Activation of complement C5 generates the potent anaphylatoxin C5a and leads to pathogen lysis, inflammation and cell damage. The therapeutic potential of C5 inhibition has been demonstrated by eculizumab, one of the world's most expensive drugs. However, the mechanism of C5 activation by C5 convertases remains elusive, thus limiting development of therapeutics. Here we identify and characterize a new protein family of tick-derived C5 inhibitors. Structures of C5 in complex with the new inhibitors, the phase I and phase II inhibitor OmCI, or an eculizumab Fab reveal three distinct binding sites on C5 that all prevent activation of C5. The positions of the inhibitor-binding sites and the ability of all three C5-inhibitor complexes to competitively inhibit the C5 convertase conflict with earlier steric-inhibition models, thus suggesting that a priming event is needed for activation. Structural basis for therapeutic inhibition of complement C5.,Jore MM, Johnson S, Sheppard D, Barber NM, Li YI, Nunn MA, Elmlund H, Lea SM Nat Struct Mol Biol. 2016 May;23(5):378-86. doi: 10.1038/nsmb.3196. Epub 2016 Mar, 28. PMID:27018802 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Complement C5 3D structures RNA uridylyltransferase

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