PDBsum entry 5c1v

Hydrolase

PDB id: 5c1v

Contents

Protein chains

317 a.a.

Ligands

PO4 ×2

Metals

_FE ×2

_ZN ×2

References listed in PDB file

Key reference

• Title: Calcineurin undergoes a conformational switch evoked via peptidyl-Prolyl isomerization.
• Authors: A.Guasch, �.�.Aranguren-Ibáñez, R.Pérez-Luque, D.Aparicio, S.Martínez-Høyer, M.C.Mulero, E.Serrano-Candelas, M.Pérez-Riba, I.Fita.
• Ref.: Plos One, 2015, 10, e0134569. [DOI no: 10.1371/journal.pone.0134569]
• PubMed id: 26248042

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.