2w08

The structure of serum amyloid P component bound to 0-phospho- threonineThe structure of serum amyloid P component bound to 0-phospho- threonine

Structural highlights 2w08 is a 5 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 1.7Å Ligands: , , 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 New therapeutic approaches in Alzheimer's disease are urgently needed. The normal plasma protein, serum amyloid P component (SAP), is always present in cerebrospinal fluid (CSF) and in the pathognomonic lesions of Alzheimer's disease, cerebrovascular and intracerebral Abeta amyloid plaques and neurofibrillary tangles, as a result of its binding to amyloid fibrils and to paired helical filaments, respectively. SAP itself may also be directly neurocytotoxic. Here, in this unique study in Alzheimer's disease of the bis(d-proline) compound, (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carb oxylic acid (CPHPC), we observed depletion of circulating SAP and also remarkable, almost complete, disappearance of SAP from the CSF. We demonstrate that SAP depletion in vivo is caused by CPHPC cross-linking pairs of SAP molecules in solution to form complexes that are immediately cleared from the plasma. We have also solved the structure of SAP complexed with phosphothreonine, its likely ligand on hyperphosphorylated tau protein. These results support further clinical study of SAP depletion in Alzheimer's disease and potentially other neurodegenerative diseases. Molecular dissection of Alzheimer's disease neuropathology by depletion of serum amyloid P component.,Kolstoe SE, Ridha BH, Bellotti V, Wang N, Robinson CV, Crutch SJ, Keir G, Kukkastenvehmas R, Gallimore JR, Hutchinson WL, Hawkins PN, Wood SP, Rossor MN, Pepys MB Proc Natl Acad Sci U S A. 2009 Apr 16. PMID:19372378 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Serum amyloid P-component

spinqualitylabelsall models 2w08, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image