User:Camille Zumstein/Sandbox

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

General structure of calcineurin:

Calcineurin is a heterodimeric Protein that consits of two subunits.

This structure presented in this article is the catalytic subunit isoform of the serine/threonine-protein phosphatase 2B, also known as calcineurin in rattus norvegicus (rat).

Localisation and expression:

Calcineurin is a cytoplasmic protein. The catalytic subunit calcineurin A, posses two major isoforms called calcineurin Aα and Aβ. the first is widely expressed among tissues whereas the other is mainly found in the lymphoid cells.Calcineurin Aβ is therefore involved in the mediation of the immune response ^[3].

Function

General structure

The phosphatase consists of 521 ^[4] aminoacids. The structure have been published 2013 by Qilu Ye et al. ^[5]. For their experiments they used x-ray diffraction. The PDB validation obtained a Resolutionof 3.0 Å, a free R-value of 0.273 and a work R-value of 0.241 ^[6].

The secondary structure includes mostly helical structures:

Mechanism of action

Addictional structural highlights

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Binding Partners

The main partners of interaction are Calmodulin,

Calcineurin is inhibited by the immunosuppressive drugs tacrolismus (FK506) or cyclosporine A (CsA). CsA and FK506 conduct their therapeutic role thought binding to the 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^[7], ^[8].

Cofactors:

Related health defects

Rheumatic diseases (arthritis):

Schizophrenia:

Diabetes: