User:Camille Zumstein/Sandbox

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 40: Line 40:
The main partners of interaction are [https://en.wikipedia.org/wiki/Calmodulin Calmodulin],NFATc1, NFATc2 and NFATc3.
The main partners of interaction are [https://en.wikipedia.org/wiki/Calmodulin Calmodulin],NFATc1, NFATc2 and NFATc3.
Many of the calcineurin substrates’ contain a PxIxIT motif. Among them, beside the phosphorylated forms of NFAT we can also mentioned; cAMP response element binding protein (CREB), PP1, microtubule-associated protein tau and glycogen synthase kinase-3 beta (GSK- 3)<ref>PMID: 17666045</ref><ref>PMID: 22676853</ref><ref>PMID:14701880</ref><ref>PMID: 7515479</ref>.
Many of the calcineurin substrates’ contain a PxIxIT motif. Among them, beside the phosphorylated forms of NFAT we can also mentioned; cAMP response element binding protein (CREB), PP1, microtubule-associated protein tau and glycogen synthase kinase-3 beta (GSK- 3)<ref>PMID: 17666045</ref><ref>PMID: 22676853</ref><ref>PMID:14701880</ref><ref>PMID: 7515479</ref>.
-
<scene name='75/750223/Can_fk506/1'>Calcineurin , here shown in complex with FK506 and FKPB (in pink on the model)</scene> is inhibited by the immunosuppressive drugs tacrolismus (<scene name='75/750223/Tacrolimus/1'>FK506</scene>) or cyclosporine A (CsA). CsA and 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>PMID: 8811062</ref>, (http://www.uptodate.com/contents/pharmacology-of-cyclosporine-and-tacrolimus).
+
<scene name='75/750223/Can_fk506/1'>Calcineurin , here shown in complex with FK506 and FKPB (in pink on the model)</scene> is inhibited by the immunosuppressive drugs tacrolismus (<scene name='75/750223/Tacrolimus/1'>FK506</scene>) or cyclosporine A (CsA). CsA and 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>PMID: 8811062</ref>, <ref>http://www.uptodate.com/contents/pharmacology-of-cyclosporine-and-tacrolimus</ref>.
 +
 
'''Cofactors''':
'''Cofactors''':
 +
Calcineurin belong to the family of [https://en.wikipedia.org/wiki/Metalloprotein metalloprotein]. To conduct its activity it requires the presence of Fe3+ and Zn2+ ions in the active site (one per subunit).Superoxide dismutase has been shown to protect calcineurin from inactivation by preventing Fe3+ from oxidation. Thus after activation of calcineurin by calmodulin, the AID is displaced from the <scene name='75/750223/Catalytic_core/1'> catalytic core,with phosphate and Fe and Zn ions bound </scene> exposing Fe3+ to oxidation <ref>PMID: 8837775</ref>(Calmodulin and Signal Transduction (p184), Linda J. Van Eldik,D. Martin Watterson (1998)).
Calcineurin belong to the family of [https://en.wikipedia.org/wiki/Metalloprotein metalloprotein]. To conduct its activity it requires the presence of Fe3+ and Zn2+ ions in the active site (one per subunit).Superoxide dismutase has been shown to protect calcineurin from inactivation by preventing Fe3+ from oxidation. Thus after activation of calcineurin by calmodulin, the AID is displaced from the <scene name='75/750223/Catalytic_core/1'> catalytic core,with phosphate and Fe and Zn ions bound </scene> exposing Fe3+ to oxidation <ref>PMID: 8837775</ref>(Calmodulin and Signal Transduction (p184), Linda J. Van Eldik,D. Martin Watterson (1998)).

Revision as of 12:16, 27 January 2017

Rat Calcineurin

PDB ID 4il1

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

Camille Zumstein

Retrieved from "http://52.214.119.220/wiki/index.php/User:Camille_Zumstein/Sandbox"
Personal tools