UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Interaction of serum amyloid P component with hexanoyl bis(D-proline) (CPHPC).

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. Green open access

[thumbnail of mn5064.pdf] PDF
mn5064.pdf

Download (1MB)

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
Downloads since deposit
94Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item