2a3w

Decameric structure of human serum amyloid P-component bound to Bis-1,2-{[(Z)-2-carboxy-2-methyl-1,3-dioxane]-5-yloxycarbamoyl}-ethane

spinqualitylabelsall models 2a3w, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2a3w 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 2.2Å Ligands: CA, CPJ Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SAMP_HUMAN Note=SAP is a precursor of amyloid component P which is found in basement membrane and associated with amyloid deposits. Function SAMP_HUMAN Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells. May also function as a calcium-dependent lectin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed A comprehensive series of solution and crystallographic studies reveal how simple, achiral, bivalent ligands of the cyclic pyruvate of glycerol promote face-to-face complex formation of the pentraxin, serum amyloid P component (SAP) into decamers. SAP, a protein of the human innate immune system, is universally present in amyloids, including cerebral amyloid deposits found in the brain of Alzheimer disease patients. Removal of SAP through a specific aggregation mechanism mediated by multivalent ligands appears to provide therapeutic benefit in the progression of this disease. Crystallographic studies reveal that in our novel series of ligands only the methyl and carboxylate moieties of the pyruvate ketal directly interact with the protein, but the geometric constraints imposed by the tether dictate which of two chair conformations are adopted by the pyruvate dioxane ring. Solution studies, as interpreted through a simple thermodynamic model, account for the distribution of pentameric and decameric bound states at different ligand concentrations and indicate that differences in the flexibility of the tether determine the geometry and stability of the specific aggregates formed between SAP and two different bivalent ligands. The factors affecting the design of ligands promoting face-to-face protein dimerization as well as potential biological implications are discussed. Ligand-assisted aggregation of proteins. Dimerization of serum amyloid P component by bivalent ligands.,Ho JG, Kitov PI, Paszkiewicz E, Sadowska J, Bundle DR, Ng KK J Biol Chem. 2005 Sep 9;280(36):31999-2008. Epub 2005 Jul 20. PMID:16036920 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serum amyloid P-component

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