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Fragment Docking to S100 Proteins Reveals a Wide Diversity of Weak Interaction Sites
Author(s) -
Arendt Yvonne,
Bhaumik Anusarka,
Del Conte Rebecca,
Luchinat Claudio,
Mori Mattia,
Porcu Marco
Publication year - 2007
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200700096
Subject(s) - heteronuclear single quantum coherence spectroscopy , docking (animal) , protein–protein interaction , small molecule , drug discovery , computational biology , plasma protein binding , binding site , chemistry , suppressor , biology , microbiology and biotechnology , stereochemistry , biochemistry , nuclear magnetic resonance spectroscopy , gene , medicine , nursing
The S100 protein family is a highly conserved group of Ca 2+ ‐binding proteins that belong to the EF‐hand type and are considered potential drug targets. In the present study we focused our attention on two members of the family: S100A13 and S100B; the former is involved in the nonclassical protein release of two proangiogenic polypeptides FGF‐1 and IL‐1α that are involved in inflammatory processes, whereas S100B is known to interact with the C‐terminal domain of the intracellular tumor suppressor p53 and promote cancer development. We screened, using waterLOGSY NMR experiments, 430 molecules of a generic fragment library and we identified different hits for each protein. The subset of fragments interacting with S100B has very few members in common with the subset interacting with S100A13. From the 15 N‐HSQC NMR spectra of the proteins in the presence of those hits the chemical shift differences Δ δ(HN) were calculated, and the main regions of surface interaction were identified. A relatively large variety of interaction regions for various ligands were identified for the two proteins, including known or suggested protein–protein interaction sites.