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Interaction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC)
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. Cooperati...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118831/ https://www.ncbi.nlm.nih.gov/pubmed/25084341 http://dx.doi.org/10.1107/S1399004714013455 |
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author | Kolstoe, Simon E. Jenvey, Michelle C. Purvis, Alan Light, Mark E. Thompson, Darren Hughes, Peter Pepys, Mark B. Wood, Stephen P. |
author_facet | Kolstoe, Simon E. Jenvey, Michelle C. Purvis, Alan Light, Mark E. Thompson, Darren Hughes, Peter Pepys, Mark B. Wood, Stephen P. |
author_sort | Kolstoe, Simon E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4118831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-41188312014-09-19 Interaction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC) Kolstoe, Simon E. Jenvey, Michelle C. Purvis, Alan Light, Mark E. Thompson, Darren Hughes, Peter Pepys, Mark B. Wood, Stephen P. Acta Crystallogr D Biol Crystallogr Research Papers 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. International Union of Crystallography 2014-07-25 /pmc/articles/PMC4118831/ /pubmed/25084341 http://dx.doi.org/10.1107/S1399004714013455 Text en © Kolstoe et al. 2014 http://creativecommons.org/licenses/by/2.0/uk/ 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. |
spellingShingle | Research Papers Kolstoe, Simon E. Jenvey, Michelle C. Purvis, Alan Light, Mark E. Thompson, Darren Hughes, Peter Pepys, Mark B. Wood, Stephen P. Interaction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC) |
title | Interaction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC) |
title_full | Interaction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC) |
title_fullStr | Interaction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC) |
title_full_unstemmed | Interaction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC) |
title_short | Interaction of serum amyloid P component with hexanoyl bis(d-proline) (CPHPC) |
title_sort | interaction of serum amyloid p component with hexanoyl bis(d-proline) (cphpc) |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118831/ https://www.ncbi.nlm.nih.gov/pubmed/25084341 http://dx.doi.org/10.1107/S1399004714013455 |
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