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The main partners of interaction are [https://en.wikipedia.org/wiki/Calmodulin Calmodulin],
The main partners of interaction are [https://en.wikipedia.org/wiki/Calmodulin Calmodulin],
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Calcineurin is inhibited by the immunosuppressive drugs tacrolismus (FK506) or cyclosporine A (CsA). CsA and FK506 conduct their therapeutic role thought binding to the [https://en.wikipedia.org/wiki/Immunophilins immunophilins] cyclophilin and FK506 binding protein (FK506BP) respectively. The complexes CsA-cyclophilin and FK506-FK506BP bind then to calcineurin in a calcium-dependent manner thus inhibiting its phosphatase activity. Therefore the addition of these drugs to lymphocytes T prevent NFAT translocation to the nucleus and the subsequent activation its target gene.That's why FK506 and CsA are use in the treatment of various immune-mediated diseases. However since calcineurin is is widely expressed in non-haemopoietic tissues like the kidney and the hearth both drug present a long term toxicity and can lead to deleterious effect to these organs<ref>https://www.ncbi.nlm.nih.gov/pubmed/8811062</ref>, <ref>http://www.uptodate.com/contents/pharmacology-of-cyclosporine-and-tacrolimus</ref>.
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Calcineurin is inhibited by the immunosuppressive drugs tacrolismus (FK506) or cyclosporine A (CsA). CsA and FK506 conduct their therapeutic role thought binding to the [https://en.wikipedia.org/wiki/Immunophilins immunophilins] cyclophilin and FK506 binding protein (FK506BP) respectively. The complexes CsA-cyclophilin and FK506-FK506BP bind then to calcineurin in a calcium-dependent manner thus inhibiting its phosphatase activity. Therefore the addition of these drugs to lymphocytes T prevent NFAT translocation to the nucleus and the subsequent activation its target gene.That's why FK506 and CsA are use in the treatment of various immune-mediated diseases. However since calcineurin is is widely expressed in non-haemopoietic tissues like the kidney and the hearth, both drugs present a long term toxicity and can lead to deleterious effect to these organs<ref>https://www.ncbi.nlm.nih.gov/pubmed/8811062</ref>, <ref>http://www.uptodate.com/contents/pharmacology-of-cyclosporine-and-tacrolimus</ref>.

Revision as of 11:14, 7 January 2017

Structure Rat Calcineurin

Caption for this structure

Drag the structure with the mouse to rotate

References

  1. ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
  2. ↑ Herraez A. Biomolecules in the computer: Jmol to the rescue. Biochem Mol Biol Educ. 2006 Jul;34(4):255-61. doi: 10.1002/bmb.2006.494034042644. PMID:21638687 doi:10.1002/bmb.2006.494034042644
  3. ↑ http://www.uniprot.org/uniprot/P63329
  4. ↑ http://www.sciencedirect.com/science/article/pii/S0898656813002702
  5. ↑ http://www.rcsb.org/pdb/explore/explore.do?structureId=4IL1
  6. ↑ https://www.ncbi.nlm.nih.gov/pubmed/8811062
  7. ↑ http://www.uptodate.com/contents/pharmacology-of-cyclosporine-and-tacrolimus

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Camille Zumstein

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