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), 371-377. (doi:10.1002/jmr.1090). (PMID:21360619).
Full text not available from this repository.
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.
|Keywords:||pentraxins, myloidosis, c-reactive protein, serum amyloid p component|
|Subjects:||Q Science > QH Natural history > QH301 Biology
Q Science > QP Physiology
|Divisions:||Faculty of Natural and Environmental Sciences > Biological Sciences
|Date Deposited:||18 Apr 2012 11:25|
|Last Modified:||26 Apr 2013 05:41|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
Actions (login required)