3l2y

The structure of C-reactive protein bound to phosphoethanolamine

spinqualitylabelsall models 3l2y, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3l2y 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 2.7Å Ligands: CA, OPE 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 The normal physiological roles of the phylogenetically conserved human plasma proteins C-reactive protein (CRP) and serum amyloid P component (SAP) are not known. Novel drugs targeting their ligand specificities are in clinical development as both proteins have significant pathophysiological effects, SAP in promoting amyloidosis and CRP in exacerbating ischemic injury. Both proteins bind to phosphoethanolamine and we show here that, under physiological conditions, phosphoethanolamine is bound with higher affinity by human SAP than by human CRP. An explanation is provided by X-ray crystal structures that show SAP residue Tyr74 allowing additional hydrophobic protein-ligand interactions compared with the equivalent Thr76 of CRP. Docking simulations show many more low energy positions for phosphoethanolamine bound by CRP than by SAP and are consistent with the crystallographic and functional binding results. These fundamental observations on structure-activity relationships will aid the design of improved pentraxin targeting drugs. Copyright (c) 2011 John Wiley & Sons, Ltd. Structural basis of ligand specificity in the human pentraxins, C-reactive protein and serum amyloid P component.,Mikolajek H, Kolstoe SE, Pye VE, Mangione P, Pepys MB, Wood SP J Mol Recognit. 2011 Mar;24(2):371-7. doi: 10.1002/jmr.1090. PMID:21360619 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also C-reactive protein

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