Blocking the interaction between S100A9 and RAGE V domain using CHAPS molecule: A novel route to drug development against cell proliferation

Chang, Chin Chi; Khan, Imran A.; Tsai, Kun Lin; Li, Hongchun; Yang, Lee Wei; Chou, Ruey Hwang; Yu, Chin

doi:10.1016/j.bbapap.2016.08.008

Cited by 33 publications

(51 citation statements)

References 64 publications

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“…We also built homology models of mouse S100A9, opossum S100A9 and chicken MRP-126 using the human S100A9 template (Figure 2 C). All these sequences could be readily accommodated in the S100 fold ( 38 ).…”

Section: Resultsmentioning

confidence: 99%

Coevolution of the Toll-Like Receptor 4 Complex with Calgranulins and Lipopolysaccharide

2018

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Toll-like receptor 4 (TLR4) induces inflammation in response to both pathogen- and host-derived molecules. Lipopolysaccharide (LPS) recognition by TLR4 has been shown to occur across the amniotes, but endogenous signaling through TLR4 has not been validated outside of placental mammals. To determine whether endogenous danger signaling is also shared across amniotes, we studied the evolution of TLR4-activation by the calgranulin proteins (S100A8, S100A9, and S100A12), a clade of host molecules that potently activate TLR4 in placental mammals. We performed phylogenetic and syntenic analysis and found MRP-126—a gene in birds and reptiles—is likely orthologous to the mammalian calgranulins. We then used an ex vivo TLR4 activation assay to establish that calgranulin pro-inflammatory activity is not specific to placental mammals, but is also exhibited by representative marsupial and sauropsid species. This activity is strongly dependent on the cofactors CD14 and MD-2 for all species studied, suggesting a conserved mode of activation across the amniotes. Ortholog complementation experiments between the calgranulins, TLR4, CD14, and MD-2 revealed extensive lineage specific-coevolution and multi-way interactions between components that are necessary for the activation of NF-κB signaling by calgranulins and LPS. Our work demonstrates that calgranulin activation of TLR4 evolved at least ~320 million years ago and has been conserved in the amniote innate immune system.

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Section: Resultsmentioning

confidence: 99%

Coevolution of the Toll-Like Receptor 4 Complex with Calgranulins and Lipopolysaccharide

2018

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“…Moreover, each monomer has the ability to bind to two calcium ions and other divalent cations such as: Zn 2+ , Cu 2+ , Mn 2+ and Fe 2+ [5,6]. The human S100A8/A9 complex has the molecular weight of 11 and 13 kDa with 93 and 114 amino acids respectively [7,8]. Various configurations of the S100A8/A9 complex are available including homodimers, heterodimers and heterotetramers which the heterodimer form has the highest stability and it is the most important agent for protein interactions [5,9,10].…”

Section: Introductionmentioning

confidence: 99%

Effects of unsaturated fatty acids (Arachidonic/Oleic Acids) on stability and structural properties of Calprotectin using molecular docking and molecular dynamics simulation approach

et al. 2020

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Calprotectin is a heterodimeric protein complex with two subunits called S100A8/A9. The protein has an essential role in inflammation process and various human diseases. It has the ability to bind to unsaturated fatty acids including Arachidonic acid, Oleic acid and etc., which could be considered as a major carrier for fatty acids. In this study we aimed to appraise the thermodynamics and structural changes of Calprotectin in presence of Arachidonic acid/Oleic acid) using docking and molecular dynami simulation method. To create the best conformation of Calprotectin-Oleic acid/Arachidonic acid complexes, the docking process was performed. The complexes with the best binding energy were selected as the models for molecular dynamics simulation process. Furthermore, the structural and thermodynamics properties of the complexes were evaluated too. The Root Mean Square Deviation and Root Mean Square Fluctuation results showed that the binding of Arachidonic acid/ Oleic acid to Calprotectin can cause the protein structural changes which was confirmed by Define Secondary Structure of Proteins results. Accordingly, the binding free energy results verified that binding of Oleic acid to Calprotectin leads to instability of S100A8/A9 subunits in the protein. Moreover, the electrostatic energy contribution of the complexes (Calprotectin-Oleic acid/Arachidonic acid) was remarkably higher than van der Waals energy. Thus, the outcome of this study confirm that Oleic acid has a stronger interaction with Calprotectin in comparison with Arachidonic acid. Our findings indicated that binding of unsaturated fatty acids to Calprotectin leads to structural changes of the S100A8/A9 subunits which could be beneficial to play a biological role in inflammation process.

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“…The human S100A9 protein was over expressed in the pET-21b vector using BL21 (DE3) as host cells. The expression and purification steps were followed as described previously [ 28 ]. The purified protein fraction was dialysed against NMR buffer (2 mM CaCl 2 , 50 mM Tris-HCl, 100 mM NaCl, 5 mM DTT, 1 mM EGTA, and 10% D 2 O, pH 7); and sample used for NMR spectroscopy 15 N-labeled S100A9.…”

Section: Methodsmentioning

confidence: 99%

“…The assignments for backbone and side-chain of S100A12 are available from the Biological Magnetic Resonance Bank (BMRB code: 19293) [ 27 ] for specific buffer conditions (100 mM NaCl, 0.02% (w/v) NaN 3 and 10 mM Hepes, pH 6.5). The assignments for S100A9 in other buffer conditions (50 mM Tris-HCl, 2mM CaCl 2 , 100 mM NaCl, 10% D 2 O pH 7.5; BMRB code: 30017) [ 28 ]. The HSQC spectra were compared with these data to assign cross-peaks in our study.…”

Section: Methodsmentioning

confidence: 99%

Blocking the interaction between S100A9 protein and RAGE V domain using S100A12 protein

Katte

2018

PLoS ONE

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The proteins S100A9 and S100A12 are associated with the human S100 calcium-binding protein family. These proteins promote interaction with target proteins and alter their conformation when they bind to calcium ions in EF-hand motifs. The V domain of RAGE (Receptor for Advanced Glycation End products) is crucial for S100A9 binding. The binding of RAGE with S100 family proteins aids in cell proliferation. In this report, we demonstrate that S100A12 protein hinders the binding of S100A9 with the RAGE V-domain. We used fluorescence and NMR spectroscopy to analyze the interaction of S100A9 with S100A12. The binary complex models of S100A9-S100A12 were developed using data obtained from 1H-15N HSQC NMR titrations and the HADDOCK program. We overlaid the complex models of S100A9-S100A12 with the same orientation of S100A9 and the RAGE V-domain. This complex showed that S100A12 protein blocks the interaction between S100A9 and the RAGE V-domain. It means S100A12 may be used as an antagonist for S100A9. The results could be favorable for developing anti-cancer drugs based on S100 family proteins.

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Blocking the interaction between S100A9 and RAGE V domain using CHAPS molecule: A novel route to drug development against cell proliferation

Cited by 33 publications

References 64 publications

Coevolution of the Toll-Like Receptor 4 Complex with Calgranulins and Lipopolysaccharide

Coevolution of the Toll-Like Receptor 4 Complex with Calgranulins and Lipopolysaccharide

Effects of unsaturated fatty acids (Arachidonic/Oleic Acids) on stability and structural properties of Calprotectin using molecular docking and molecular dynamics simulation approach

Blocking the interaction between S100A9 protein and RAGE V domain using S100A12 protein

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