5C1V: Crystal Structure Analysis Of Catalytic Subunit Of Human Calcineurin

Citation:
Abstract
A limited repertoire of PPP family of serine/threonine phosphatases with a highly conserved catalytic domain acts on thousands of protein targets to orchestrate myriad central biological roles. A major structural reorganization of human calcineurin, a ubiquitous Ser/Thr PPP regulated by calcium and calmodulin and targeted by immunosuppressant drugs cyclosporin A and FK506, is unveiled here. The new conformation involves trans- to cis-isomerization of proline in the SAPNY sequence, highly conserved across PPPs, and remodels the main regulatory site where NFATc transcription factors bind. Transitions between cis- and trans-conformations may involve peptidyl prolyl isomerases such as cyclophilin A and FKBP12, which are known to physically interact with and modulate calcineurin even in the absence of immunosuppressant drugs. Alternative conformations in PPPs provide a new perspective on interactions with substrates and other protein partners and may foster development of more specific inhibitors as drug candidates.
PDB ID: 5C1VDownload
MMDB ID: 136194
PDB Deposition Date: 2015/6/15
Updated in MMDB: 2016/02
Experimental Method:
x-ray diffraction
Resolution: 3.35  Å
Source Organism:
Similar Structures:
Biological Unit for 5C1V: monomeric; determined by author
Molecular Components in 5C1V
Label Count Molecule
Protein (1 molecule)
1
Serine/threonine-protein Phosphatase 2B Catalytic Subunit Alpha Isoform(Gene symbol: PPP3CA)
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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