7tba

Pentraxin - ligand complexPentraxin - ligand complex

Structural highlights 7tba is a 20 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 3.5Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CRP_HUMAN Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine. Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells. Publication Abstract from PubMed C-reactive protein (CRP) is an early-stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric CRP (pCRP) structure to a pentameric CRP intermediate (pCRP*) and ultimately to the monomeric CRP (mCRP) form, both exhibiting highly pro-inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X-ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provide in vitro and in vivo proof-of-concept data demonstrating that the low molecular weight tool compound inhibits CRP-driven exacerbation of local inflammatory responses, while potentially preserving pathogen-defense functions of CRP. The inhibition of the conformational change generating pro-inflammatory CRP isoforms via phosphocholine-mimicking compounds represents a promising, potentially broadly applicable anti-inflammatory therapy. A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change in C-reactive protein.,Zeller J, Cheung Tung Shing KS, Nero TL, McFadyen JD, Krippner G, Bogner B, Kreuzaler S, Kiefer J, Horner VK, Braig D, Danish H, Baratchi S, Fricke M, Wang X, Kather MG, Kammerer B, Woollard KJ, Sharma P, Morton CJ, Pietersz G, Parker MW, Peter K, Eisenhardt SU EMBO Mol Med. 2023 Jan 11;15(1):e16236. doi: 10.15252/emmm.202216236. Epub 2022 , Dec 5. PMID:36468184 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also C-reactive protein

spinqualitylabelsall models 7tba, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image