4AYU

Structure of N-Acetyl-D-Proline bound to serum amyloid P component

Summary for 4AYU

• Entry DOI: 10.2210/pdb4ayu/pdb
• Related: 1GYK 1LGN 1SAC 2A3W 2A3X 2A3Y 2W08 4AVS 4AVT 4AVV
• Descriptor: SERUM AMYLOID P-COMPONENT, CALCIUM ION, N-ACETYL-D-PROLINE, ... (6 entities in total)
• Functional Keywords: sugar binding protein, lectin
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 5
• Total formula weight: 119165.40

Authors

Hughes, P.,Kolstoe, S.E.,Wood, S.P. (deposition date: 2012-06-22, release date: 2013-07-10, Last modification date: 2024-10-23)

Primary citation

Kolstoe, S.E.,Jenvey, M.C.,Purvis, A.,Light, M.E.,Thompson, D.,Hughes, P.,Pepys, M.B.,Wood, S.P.
Interaction of Serum Amyloid P Component with Hexanoyl Bis(D-Proline) (Cphpc)
Acta Crystallogr.,Sect.D, 70:2232-, 2014

PubMed 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.

PubMed: 25084341
DOI: 10.1107/S1399004714013455

Experimental method

X-RAY DIFFRACTION (1.5 Å)