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

DOI: 10.1107/S1399004714013455 DOI Help
PMID: 25084341 PMID Help

Authors: Simon Kolstoe (UCL) , Michelle C. Jenvey (School of Biological Sciences, University of Southampton) , Alan Purvis (Department of Life Sciences, Imperial College London) , Mark Light (University of Southampton) , Darren Thompson (School of Life Sciences, University of Sussex) , Peter Hughes (University College London) , Mark B. Pepys (University College London) , Stephen Wood (University College London)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Biological Crystallography , VOL 70 , PAGES 2232 - 2240

State: Published (Approved)
Published: August 2014
Diamond Proposal Number(s): 8922

Open Access Open Access

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.

Journal Keywords: serum amyloid P component; CPHPC; amyloidosis

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography

Other Facilities: ESRF (ID14-1 and ID14-2)