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Predicting the disruption by UO 2 2+ of a protein‐ligand interaction
Author(s) -
Pible Olivier,
Vidaud Claude,
Plantevin Sophie,
Pellequer JeanLuc,
Quéméneur Eric
Publication year - 2010
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.501
Subject(s) - chemistry , uranyl , phosphorylcholine , binding site , ligand (biochemistry) , calcium , surface plasmon resonance , molecule , crystallography , calcium binding protein , plasma protein binding , biophysics , biochemistry , ion , biology , materials science , nanotechnology , receptor , organic chemistry , nanoparticle
The uranyl cation (UO 2 2+ ) can be suspected to interfere with the binding of essential metal cations to proteins, underlying some mechanisms of toxicity. A dedicated computational screen was used to identify UO 2 2+ binding sites within a set of nonredundant protein structures. The list of potential targets was compared to data from a small molecules interaction database to pinpoint specific examples where UO 2 2+ should be able to bind in the vicinity of an essential cation, and would be likely to affect the function of the corresponding protein. The C‐reactive protein appeared as an interesting hit since its structure involves critical calcium ions in the binding of phosphorylcholine. Biochemical experiments confirmed the predicted binding site for UO 2 2+ and it was demonstrated by surface plasmon resonance assays that UO 2 2+ binding to CRP prevents the calcium‐mediated binding of phosphorylcholine. Strikingly, the apparent affinity of UO 2 2+ for native CRP was almost 100‐fold higher than that of Ca 2+ . This result exemplifies in the case of CRP the capability of our computational tool to predict effective binding sites for UO 2 2+ in proteins and is a first evidence of calcium substitution by the uranyl cation in a native protein.