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Structural basis of ligand specificity in the human pentraxins, C-reactive protein and serum amyloid P component

Mikolajek, Halina, Kolstoe, Simon E., Pye, Valerie E., Mangione, Palma, Pepys, Mark B. and Wood, Stephen P. (2011) Structural basis of ligand specificity in the human pentraxins, C-reactive protein and serum amyloid P component Journal of Molecular Recognition, 24, (2), pp. 371-377. (doi:10.1002/jmr.1090). (PMID:21360619).

Record type: Article

Abstract

The normal physiological roles of the phylogenetically conserved human plasma proteins C-reactive protein (CRP) and serum amyloid P component (SAP) are not known. Novel drugs targeting their ligand specificities are in clinical development as both proteins have significant pathophysiological effects, SAP in promoting amyloidosis and CRP in exacerbating ischemic injury. Both proteins bind to phosphoethanolamine and we show here that, under physiological conditions, phosphoethanolamine is bound with higher affinity by human SAP than by human CRP. An explanation is provided by X-ray crystal structures that show SAP residue Tyr74 allowing additional hydrophobic protein–ligand interactions compared with the equivalent Thr76 of CRP. Docking simulations show many more low energy positions for phosphoethanolamine bound by CRP than by SAP and are consistent with the crystallographic and functional binding results. These fundamental observations on structure–activity relationships will aid the design of improved pentraxin targeting drugs.

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More information

e-pub ahead of print date: 25 February 2011
Published date: March 2011
Keywords: pentraxins, myloidosis, c-reactive protein, serum amyloid p component
Organisations: Centre for Biological Sciences

Identifiers

Local EPrints ID: 337109
URI: http://eprints.soton.ac.uk/id/eprint/337109
ISSN: 0952-3499
PURE UUID: 8e7b7a6d-69d7-4614-9f3e-5b50cd3e5dda
ORCID for Halina Mikolajek: ORCID iD orcid.org/0000-0003-0776-9974

Catalogue record

Date deposited: 18 Apr 2012 11:25
Last modified: 18 Jul 2017 06:04

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Contributors

Author: Simon E. Kolstoe
Author: Valerie E. Pye
Author: Palma Mangione
Author: Mark B. Pepys
Author: Stephen P. Wood

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