2W08

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

2W08 の概要

• エントリーDOI: 10.2210/pdb2w08/pdb
• 関連するPDBエントリー: 1GYK 1LGN 1SAC 2A3W 2A3X 2A3Y
• 分子名称: SERUM AMYLOID P-COMPONENT, CALCIUM ION, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: glycoprotein, polymorphism, metal-binding, tau, lectin, calcium, amyloid, secreted, alzheimers
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 118914.59

構造登録者

Kolstoe, S.E.,Pepys, M.B.,Wood, S.P. (登録日: 2008-08-12, 公開日: 2009-04-14, 最終更新日: 2024-10-23)

主引用文献

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

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: 19372378
DOI: 10.1073/PNAS.0902640106

実験手法

X-RAY DIFFRACTION (1.7 Å)