Kolstoe, SE;
Jenvey, MC;
Purvis, A;
Light, ME;
Thompson, D;
Hughes, P;
Pepys, MB;
(2014)
Interaction of serum amyloid P component with hexanoyl bis(D-proline) (CPHPC).
Acta Crystallogr D Biol Crystallogr
, 70
( 8)
2232 - 2240.
10.1107/S1399004714013455.
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Abstract
Under physiological conditions, the pentameric human plasma protein serum amyloid P component (SAP) binds hexanoyl bis(D-proline) (R-1-{6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl}pyrrolidine-2-carboxylic acid; CPHPC) through its D-proline head groups in a calcium-dependent interaction. Cooperative effects in binding lead to a substantial enhancement of affinity. Five molecules of the bivalent ligand cross-link and stabilize pairs of SAP molecules, forming a decameric complex that is rapidly cleared from the circulation by the liver. Here, it is reported that X-ray analysis of the SAP complex with CPHPC and cadmium ions provides higher resolution detail of the interaction than is observed with calcium ions. Conformational isomers of CPHPC observed in solution by HPLC and by X-ray analysis are compared with the protein-bound form. These are discussed in relation to the development of CPHPC to provide SAP depletion for the treatment of amyloidosis and other indications.
| Type: | Article |
|---|---|
| Title: | Interaction of serum amyloid P component with hexanoyl bis(D-proline) (CPHPC). |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1107/S1399004714013455 |
| Publisher version: | http://dx.doi.org/10.1107/S1399004714013455 |
| Language: | English |
| Additional information: | This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. |
| Keywords: | CPHPC, amyloidosis, serum amyloid P component, Calcium, Calorimetry, Chromatography, High Pressure Liquid, Crystallography, X-Ray, Proline, Protein Conformation, Serum Amyloid P-Component, Thermodynamics |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1437140 |
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