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User:Camille Zumstein/Sandbox
From Proteopedia
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'''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)). | ||
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== Related health defects == | == Related health defects == | ||
Calcineurin hyperactivation thought dysregulation of the Ca2+ dynamic have been show to play a critical role in several diseases like Rheumatoid arthritis (RA), Schizophrenia ,Diabetes, Systemic Lupus Erythematosus as well as Alzheimer diseases(AD) (http://www.uptodate.com/contents/pharmacology-of-cyclosporine-and-tacrolimus)<ref>PMID: 12851457</ref><ref>PMID: 16988714</ref><ref>PMID:20421909</ref>. | Calcineurin hyperactivation thought dysregulation of the Ca2+ dynamic have been show to play a critical role in several diseases like Rheumatoid arthritis (RA), Schizophrenia ,Diabetes, Systemic Lupus Erythematosus as well as Alzheimer diseases(AD) (http://www.uptodate.com/contents/pharmacology-of-cyclosporine-and-tacrolimus)<ref>PMID: 12851457</ref><ref>PMID: 16988714</ref><ref>PMID:20421909</ref>. | ||
Taking the example of AD which is a age-related memory dysfunction ; it it know that in older organism the brain is less plastic due to a dysregulation of Ca2+ dynamic. This in addition to the presence of oligomeric Aß is sufficient to explain an enhancement of CaN activity leading to severals symptoms like decreased neurotransmission , synaptic loss , neuroinflammation ...<ref>PMID: 22654726</ref>Therefore calmodulin inhibitors are potential alternatives against Alzheimer diseases. | Taking the example of AD which is a age-related memory dysfunction ; it it know that in older organism the brain is less plastic due to a dysregulation of Ca2+ dynamic. This in addition to the presence of oligomeric Aß is sufficient to explain an enhancement of CaN activity leading to severals symptoms like decreased neurotransmission , synaptic loss , neuroinflammation ...<ref>PMID: 22654726</ref>Therefore calmodulin inhibitors are potential alternatives against Alzheimer diseases. | ||
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== Human/Rat calcineurin comparison == | == Human/Rat calcineurin comparison == | ||
| - | [http://www.uniprot.org/uniprot/Q08209 Human] and [http://www.uniprot.org/uniprot/P63329 Rat] calcineurin have the same function and global structure [[Image:Human rat comparison.PNG|thumb|upright= | + | [http://www.uniprot.org/uniprot/Q08209 Human] and [http://www.uniprot.org/uniprot/P63329 Rat] calcineurin have the same function and global structure [[Image:Human rat comparison.PNG|thumb|upright=3|left| Structure of rat calcineurin and human calcineurin ]]. |
The size (521 amino acids) and subunits of the linear structure are the same, as well as the 3D structure. | The size (521 amino acids) and subunits of the linear structure are the same, as well as the 3D structure. | ||
<br style="clear:both" /> | <br style="clear:both" /> | ||
| - | + | [[Image:Proteopedia.PNG|thumb|upright=4|right| Structure of human calcineurin (up) and rat calcineurin (down) ]] However, there are a few differences, such as the secondary structures. | |
For instance, Human Calcineurin has one Beta strand at <scene name='75/750223/Residues_11-13_beta_strand/1'>residues 11-13</scene> whereas Rat Calcineurin has not. | For instance, Human Calcineurin has one Beta strand at <scene name='75/750223/Residues_11-13_beta_strand/1'>residues 11-13</scene> whereas Rat Calcineurin has not. | ||
Indeed, Calcineurin is a highly conserved protein from yeast to mammals. | Indeed, Calcineurin is a highly conserved protein from yeast to mammals. | ||
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== Evolutionary conservation == | == Evolutionary conservation == | ||
'''Calcineurin A''' | '''Calcineurin A''' | ||
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This high degree of conservation allows functional interchange of calcineurin B subunits between eukaryotic species. <ref name="paper" /> | This high degree of conservation allows functional interchange of calcineurin B subunits between eukaryotic species. <ref name="paper" /> | ||
<br style="clear:both" /> | <br style="clear:both" /> | ||
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== Calcineurin history == | == Calcineurin history == | ||
Calcineurin was first detected by Wang and Desai in 1976 as a column fraction that inhibited the calmodulin-dependent cyclic nucleotide phosphodiesterase. | Calcineurin was first detected by Wang and Desai in 1976 as a column fraction that inhibited the calmodulin-dependent cyclic nucleotide phosphodiesterase. | ||
Revision as of 12:07, 27 January 2017
Rat Calcineurin
Rat Calcineurin
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