2W08
The structure of serum amyloid P component bound to 0-phospho- threonine
Summary for 2W08
| Entry DOI | 10.2210/pdb2w08/pdb |
| Related | 1GYK 1LGN 1SAC 2A3W 2A3X 2A3Y |
| Descriptor | SERUM AMYLOID P-COMPONENT, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total) |
| Functional Keywords | glycoprotein, polymorphism, metal-binding, tau, lectin, calcium, amyloid, secreted, alzheimers |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 5 |
| Total formula weight | 118914.59 |
| Authors | Kolstoe, S.E.,Pepys, M.B.,Wood, S.P. (deposition date: 2008-08-12, release date: 2009-04-14, Last modification date: 2024-10-23) |
| Primary citation | Kolstoe, S.E.,Ridha, B.H.,Bellotti, V.,Wang, N.,Robinson, C.V.,Crutch, S.J.,Keir, G.,Kukkastenvehmas, R.,Gallimore, J.R.,Hutchinson, W.L.,Hawkins, P.N.,Wood, S.P.,Rossor, M.N.,Pepys, M.B. Molecular Dissection of Alzheimer'S Disease Neuropathology by Depletion of Serum Amyloid P Component. Proc.Natl.Acad.Sci.USA, 106:7619-, 2009 Cited by PubMed Abstract: 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-carboxylic 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. PubMed: 19372378DOI: 10.1073/PNAS.0902640106 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.7 Å) |
Structure validation
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