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

Kolstoe Simon E.; Jenvey Michelle C.; Purvis AlanLight Mark E.Thompson DarrenHughes PeterPepys Mark B.Wood Stephen P.

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

机译：血清淀粉样蛋白P组件的交互hexanoyl之二(D-proline CPHPC)

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摘要

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.

机译：在生理条件下,pentameric人血浆蛋白血清淀粉样蛋白P组件(SAP)结合己酰bis (D-proline)

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来源
《Acta crystallographica.Section D. Biological crystallography》 |2014年第8期|2232-2240|共9页
作者
Kolstoe Simon E.; Jenvey Michelle C.; Purvis AlanLight Mark E.Thompson DarrenHughes PeterPepys Mark B.Wood Stephen P.;
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作者单位

UCL, Ctr Amyloidosis & Acute Phase Prot, Lab Prot Crystallog, Wolfson Drug Discovery Unit,Div Med;

Univ Southampton, Sch Chem, UK Natl Crystallog Serv, Southampton SO17 1BJ, Hants, England;

Univ Sussex, Sch Life Sci, Brighton BN1 9RQ, E Sussex, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Life Sci, London SW7 2AZ, EnglandUniv Southampton, Sch Biol Sci, Southampton SO17 1BJ, Hants, England;

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原文格式 PDF
正文语种英语
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关键词
APCS gene; X-ray analysis; Amyloid P ComponentSerum ProteinLiver CirculationCalcium CationAmyloidosis;

机译：apc基因;x射线分析;淀粉样蛋白P ComponentSerumProteinLiver CirculationCalcium CationAmyloidosis;

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

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