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

DOI: 10.1107/S1399004714013455
PMID: 25084341

Authors: Simon E. Kolstoe (University College London) , Michelle C. Jenvey (University of Southampton) , Alan Purvis (Imperial College London) , Mark E. Light (University of Southampton) , Darren Thompson (University of Sussex) , Peter Hughes (University College London) , Mark B. Pepys (University College London) , Stephen P. 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

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

Diamond Keywords: Amyloidosis

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

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

Added On: 25/09/2014 15:52

Documents:
mn5064.pdf

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)