Cis-trans proline isomers in the catalytic domain of calcineurin.

Autor: Teixeira JMC; BioNMR Laboratory, Inorganic and Organic Chemistry Department, University of Barcelona, Spain., Guasch A; Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Parc Científic, Barcelona, Spain., Biçer A; Cell Signalling Unit, Genes, Disease and Therapy Program, Human Molecular Genetics Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Aranguren-Ibáñez Á; Cell Signalling Unit, Genes, Disease and Therapy Program, Human Molecular Genetics Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Chashmniam S; BioNMR Laboratory, Inorganic and Organic Chemistry Department, University of Barcelona, Spain., Paniagua JC; Department of Material Science and Physical Chemistry, Institut de Química Teòrica i Computacional (IQTC-UB), University of Barcelona, Spain., Pérez-Riba M; Cell Signalling Unit, Genes, Disease and Therapy Program, Human Molecular Genetics Laboratory, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain., Fita I; Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Parc Científic, Barcelona, Spain., Pons M; BioNMR Laboratory, Inorganic and Organic Chemistry Department, University of Barcelona, Spain.
Jazyk: angličtina
Zdroj: The FEBS journal [FEBS J] 2019 Mar; Vol. 286 (6), pp. 1230-1239. Date of Electronic Publication: 2018 Dec 31.
DOI: 10.1111/febs.14721
Abstrakt: Calcineurin is an essential calcium-activated serine/threonine phosphatase. The six NMR-observable methionine methyl groups in the catalytic domain of human calcineurin Aα (CNA) were assigned and used as reporters of the presence of potential cis-trans isomers in solution. Proline 84 is found in the cis conformation in most calcineurin X-ray structures, and proline 309, which is part of a highly conserved motif in phosphoprotein phosphatases, was modeled with a cis peptide bond in one of the two molecules present in the asymmetric unit of CNA. We mutated each of the two prolines to alanine to force the trans conformation. Solution NMR shows that the P84A CNA mutant exists in two forms, compatible with cis-trans isomers, while the P309A mutant is predominantly in the trans conformation. DATABASE: PDB depositions mentioned PDB 5C1V and 2JOG.
(© 2018 Federation of European Biochemical Societies.)
Databáze: MEDLINE
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