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Cis-trans proline isomers in the catalytic domain of calcineurin

Teixeira, J. M. C ; Sharif University of Technology | 2019

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  1. Type of Document: Article
  2. DOI: 10.1111/febs.14721
  3. Publisher: Blackwell Publishing Ltd , 2019
  4. Abstract:
  5. 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
  6. Keywords:
  7. 13 C-methyl methionine NMR ; Cis-trans isomerization ; NMR ; Alanine ; Phosphatase ; Transcription factor NFAT ; PPP3CA protein, human ; Enzyme activity ; Heteronuclear single quantum coherence ; Isomerization ; Molecular model ; Priority journal ; Protein domain ; Protein motif ; Proton nuclear magnetic resonance ; Structure analysis ; X ray analysis ; Chemistry ; Enzyme active site ; Genetics ; Metabolism ; Amino Acid Sequence ; Calcineurin ; Catalytic Domain ; Methionine ; Mutation ; Proline ; Protein Conformation ; Stereoisomerism
  8. Source: FEBS Journal ; Volume 286, Issue 6 , 2019 , Pages 1230-1239 ; 1742464X (ISSN)
  9. URL: https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14721