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Annexin A2 complexes with S100 proteins: structure, function and pharmacological manipulation.

Liu Y, Myrvang HK, Dekker LV - Br. J. Pharmacol. (2014)

Bottom Line: The interaction between AnxA2 and S100A10 has been very well characterized historically; more recently, other S100 proteins have been shown to interact with AnxA2 as well.The biochemical evidence for the occurrence of these protein interactions will be discussed, as well as their function.Recent studies aiming to generate inhibitors of S100 protein interactions will be described and the potential of these inhibitors to further our understanding of AnxA2 S100 protein interactions will be discussed.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.

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Chemical structures of S100 protein interaction inhibitors.
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fig03: Chemical structures of S100 protein interaction inhibitors.

Mentions: A receptor-guided as well as a ligand-guided virtual screening approach was recently used to identify a novel class of small molecules that inhibit the interaction between AnxA2 and S100A10 (Reddy et al., 2011; 2012; 2014,,) (Figure 3). This virtual screening approach allowed the identification of candidate blockers that were able to dock into the AnxA2-binding site on S100A10 or that mimicked the binding pose of the AnxA2 N-terminus as defined in the complex crystal structure (Rety et al., 1999). Candidate molecules were then screened in a biochemical FRET assay that measured the binding between the AnxA2 N-terminus and the S100A10 protein. This identified two classes of compounds: 3-hydroxy-1H-pyrrol-2(5H)-one analogues and substituted 1,2,4-triazoles as effective blockers of the binding of S100A10 and AnxA2 (Reddy et al., 2011; 2012). The docking suggested that both kinds of inhibitors could bind to three pockets on S100A10 that are normally occupied by an acetyl, valine and leucine moiety on the AnxA2 N-terminus (Reddy et al., 2011; 2012,). Selected blockers were also able to inhibit the interaction of the native complex of AnxA2 and S100A10 and some were shown to inhibit the complex inside the cell. These compounds may be used to further elucidate the function of the (S100A10-AnxA2)2 complex.


Annexin A2 complexes with S100 proteins: structure, function and pharmacological manipulation.

Liu Y, Myrvang HK, Dekker LV - Br. J. Pharmacol. (2014)

Chemical structures of S100 protein interaction inhibitors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376447&req=5

fig03: Chemical structures of S100 protein interaction inhibitors.
Mentions: A receptor-guided as well as a ligand-guided virtual screening approach was recently used to identify a novel class of small molecules that inhibit the interaction between AnxA2 and S100A10 (Reddy et al., 2011; 2012; 2014,,) (Figure 3). This virtual screening approach allowed the identification of candidate blockers that were able to dock into the AnxA2-binding site on S100A10 or that mimicked the binding pose of the AnxA2 N-terminus as defined in the complex crystal structure (Rety et al., 1999). Candidate molecules were then screened in a biochemical FRET assay that measured the binding between the AnxA2 N-terminus and the S100A10 protein. This identified two classes of compounds: 3-hydroxy-1H-pyrrol-2(5H)-one analogues and substituted 1,2,4-triazoles as effective blockers of the binding of S100A10 and AnxA2 (Reddy et al., 2011; 2012). The docking suggested that both kinds of inhibitors could bind to three pockets on S100A10 that are normally occupied by an acetyl, valine and leucine moiety on the AnxA2 N-terminus (Reddy et al., 2011; 2012,). Selected blockers were also able to inhibit the interaction of the native complex of AnxA2 and S100A10 and some were shown to inhibit the complex inside the cell. These compounds may be used to further elucidate the function of the (S100A10-AnxA2)2 complex.

Bottom Line: The interaction between AnxA2 and S100A10 has been very well characterized historically; more recently, other S100 proteins have been shown to interact with AnxA2 as well.The biochemical evidence for the occurrence of these protein interactions will be discussed, as well as their function.Recent studies aiming to generate inhibitors of S100 protein interactions will be described and the potential of these inhibitors to further our understanding of AnxA2 S100 protein interactions will be discussed.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.

Show MeSH
Related in: MedlinePlus