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


Journal

The FEBS journal
ISSN: 1742-4658
Titre abrégé: FEBS J
Pays: England
ID NLM: 101229646

Informations de publication

Date de publication:
03 2019
Historique:
received: 23 07 2018
revised: 06 11 2018
accepted: 03 12 2018
pubmed: 12 12 2018
medline: 1 5 2020
entrez: 12 12 2018
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30536857
doi: 10.1111/febs.14721
doi:

Substances chimiques

Proline 9DLQ4CIU6V
Methionine AE28F7PNPL
Calcineurin EC 3.1.3.16
PPP3CA protein, human EC 3.1.3.16

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1230-1239

Informations de copyright

© 2018 Federation of European Biochemical Societies.

Auteurs

João M C Teixeira (JMC)

BioNMR Laboratory, Inorganic and Organic Chemistry Department, University of Barcelona, Spain.

Alicia Guasch (A)

Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Parc Científic, Barcelona, Spain.

Atilla 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.

Álvaro 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.

Saeed Chashmniam (S)

BioNMR Laboratory, Inorganic and Organic Chemistry Department, University of Barcelona, Spain.

Juan Carlos Paniagua (JC)

Department of Material Science and Physical Chemistry, Institut de Química Teòrica i Computacional (IQTC-UB), University of Barcelona, Spain.

Mercè 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.

Ignacio Fita (I)

Institut de Biologia Molecular de Barcelona (IBMB-CSIC), Parc Científic, Barcelona, Spain.

Miquel Pons (M)

BioNMR Laboratory, Inorganic and Organic Chemistry Department, University of Barcelona, Spain.

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Classifications MeSH