Guasch, AliciaAranguren Ibáñez, ÁlvaroPérez Luque, RosaAparicio, DavidMartínez Høyer, SergioMulero Roig, María CarmenSerrano Candelas, Eva, 1982-Pérez Riba, MercèFita Rodríguez, Ignasi2016-03-102016-03-102015-08-061932-6203https://hdl.handle.net/2445/96367A 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.15 p.application/pdfengcc-by (c) Guasch et al., 2015http://creativecommons.org/licenses/by/3.0/esEstructura cristal·lina (Sòlids)EsterasesSíntesi de pèptidsIsomeritzacióInteraccions dels medicamentsLayer structure (Solids)EsterasesPeptide synthesisIsomerizationDrug interactionsinfo:eu-repo/semantics/article6579672016-03-10info:eu-repo/semantics/openAccess26248042