3L2Y
The structure of C-reactive protein bound to phosphoethanolamine
Summary for 3L2Y
| Entry DOI | 10.2210/pdb3l2y/pdb |
| Related | 1B09 1GNH 1LJ7 |
| Descriptor | C-reactive protein, CALCIUM ION, PHOSPHORIC ACID MONO-(2-AMINO-ETHYL) ESTER, ... (4 entities in total) |
| Functional Keywords | pentraxin, acute phase reactant, immune system, phosphoethanolamine, acute phase, metal-binding, pyrrolidone carboxylic acid, secreted, calcium-binding protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Secreted: P02741 |
| Total number of polymer chains | 20 |
| Total formula weight | 465785.16 |
| Authors | Mikolajek, H.,Kolstoe, S.E.,Wood, S.P.,Pepys, M.B. (deposition date: 2009-12-15, 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 Cited by 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: 21360619DOI: 10.1002/jmr.1090 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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