ArticleBiochemistry2009
Small molecules bound to unique sites in the target protein binding cleft of calcium-bound S100B as characterized by nuclear magnetic resonance and X-ray crystallography.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Secondary Modification of S100B Influences Anti Amyloid-β Aggregation Activity and Alzheimer's Disease Pathology.International journal of molecular sciences · 2024Article
- Article
- The calcium-binding protein S100B reduces IL6 production in malignant melanoma via inhibition of RSK cellular signaling.PloS one · 2021Article
- S100 proteins in rheumatic diseases.Nature reviews. Rheumatology · 2018Review
- Structural Basis for S100B Interaction with its Target Proteins.Journal of molecular and genetic medicine : an international journal of biomedical research · 2018Article
- X-ray crystal structure of human calcium-bound S100A1.Acta crystallographica. Section F, Structural biology communications · 2017Article
- Binding of transition metals to S100 proteins.Science China. Life sciences · 2016Review
- Novel protein-inhibitor interactions in site 3 of Ca(2+)-bound S100B as discovered by X-ray crystallography.Acta crystallographica. Section D, Structural biology · 2016Article
- Fluorescence polarization assays in high-throughput screening and drug discovery: a review.Methods and applications in fluorescence · 2016Article
- Small Molecule Inhibitors of Ca(2+)-S100B Reveal Two Protein Conformations.Journal of medicinal chemistry · 2016Article
- Covalent small molecule inhibitors of Ca(2+)-bound S100B.Biochemistry · 2014Article
- In vivo screening of S100B inhibitors for melanoma therapy.Methods in molecular biology (Clifton, N.J.) · 2013Article
- The evolution of S100B inhibitors for the treatment of malignant melanoma.Future medicinal chemistry · 2013Review
- Functions of S100 proteins.Current molecular medicine · 2013Review
- Modulating protein-protein interactions with small molecules: the importance of binding hotspots.Journal of molecular biology · 2012Article
- What can we learn from the evolution of protein-ligand interactions to aid the design of new therapeutics?PloS one · 2012Article
- Molecular dynamic simulation insights into the normal state and restoration of p53 function.International journal of molecular sciences · 2012Review
- In vitro screening and structural characterization of inhibitors of the S100B-p53 interaction.International journal of high throughput screening · 2010Article
- The Calcium-Dependent Interaction of S100B with Its Protein Targets.Cardiovascular psychiatry and neurology · 2010Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Structural studies are part of a rational drug design program aimed at inhibiting the S100B-p53 interaction and restoring wild-type p53 function in malignant melanoma. To this end, structures of three compounds (SBi132, SBi1279, and SBi523) bound to Ca(2+)-S100B were determined by X-ray crystallography at 2.10 A (R(free) = 0.257), 1.98 A (R(free) = 0.281), and 1.90 A (R(free) = 0.228) resolution, respectively. Upon comparison, SBi132, SBi279, and SBi523 were found to bind in distinct locations and orientations within the hydrophobic target binding pocket of Ca(2+)-S100B with minimal structural changes observed for the protein upon complex formation with each compound. Specifically, SBi132 binds nearby residues in loop 2 (His-42, Phe-43, and Leu-44) and helix 4 (Phe-76, Met-79, Ile-80, Ala-83, Cys-84, Phe-87, and Phe-88), whereas SBi523 interacts with a separate site defined by residues within loop 2 (Ser-41, His-42, Phe-43, Leu-44, Glu-45, and Glu-46) and one residue on helix 4 (Phe-87). The SBi279 binding site on Ca(2+)-S100B overlaps the SBi132 and SBi523 sites and contacts residues in both loop 2 (Ser-41, His-42, Phe-43, Leu-44, and Glu-45) and helix 4 (Ile-80, Ala-83, Cys-84, Phe-87, and Phe-88). NMR data, including saturation transfer difference (STD) and (15)N backbone and (13)C side chain chemical shift perturbations, were consistent with the X-ray crystal structures and demonstrated the relevance of all three small molecule-S100B complexes in solution. The discovery that SBi132, SBi279, and SBi523 bind to proximal sites on Ca(2+)-S100B could be useful for the development of a new class of molecule(s) that interacts with one or more of these binding sites simultaneously, thereby yielding novel tight binding inhibitors specific for blocking protein-protein interactions involving S100B.
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