3KQR

The structure of serum amyloid p component bound to phosphoethanolamine

Summary for 3KQR

• Entry DOI: 10.2210/pdb3kqr/pdb
• Related: 1GYK 1LGN 1SAC 2A3W 2A3X 2A3Y
• Descriptor: Serum amyloid P-component, PHOSPHORIC ACID MONO-(2-AMINO-ETHYL) ESTER, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: glycoprotein, amyloid, disulfide bond, lectin, metal-binding, secreted
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 5
• Total formula weight: 118624.41

Authors

Mikolajek, H.,Kolstoe, S.E.,Wood, S.P.,Pepys, M.B. (deposition date: 2009-11-17, release date: 2010-12-08, Last modification date: 2025-03-26)

Primary citation

Mikolajek, H.,Kolstoe, S.E.,Pye, V.E.,Mangione, P.,Pepys, M.B.,Wood, S.P.
Structural basis of ligand specificity in the human pentraxins, C-reactive protein and serum amyloid P component.
J.Mol.Recognit., 24:371-377, 2011

PubMed 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.

PubMed: 21360619
DOI: 10.1002/jmr.1090

Experimental method

X-RAY DIFFRACTION (1.5 Å)