Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Calcineurin. Structure, function, and inhibition.

C S Hemenway1, J Heitman

  • 1Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, USA.

Cell Biochemistry and Biophysics
|April 1, 1999
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Genome variation in Cryptococcus gattii, an emerging pathogen of immunocompetent hosts.

mBio·2011
Same author

Isolation of Cryptococcus gattii and Cryptococcus neoformans var. grubii from the flowers and bark of Eucalyptus trees in India.

Medical mycology·2005
Same author

The synthetic peptide PFWT disrupts AF4-AF9 protein complexes and induces apoptosis in t(4;11) leukemia cells.

Leukemia·2004
Same author

Cryptococcus neoformans shows a remarkable genotypic diversity in Brazil.

Journal of clinical microbiology·2004
Same author

MLL fusion partners AF4 and AF9 interact at subnuclear foci.

Leukemia·2003
Same author

The TOR signal transduction cascade controls cellular differentiation in response to nutrients.

Molecular biology of the cell·2001
Same journal

From Isoprene Units to Polyprenols and Dolichols: 70 Years of Polyisoprenoid Biosynthesis Research.

Cell biochemistry and biophysics·2026
Same journal

Therapeutic Insights into the Hepatoprotective Effect of Strobilanthes callosa.

Cell biochemistry and biophysics·2026
Same journal

The Dual Role of TGF-β and Hypoxia on MMP14-Mediated Invasion in PC3 Cells.

Cell biochemistry and biophysics·2026
Same journal

Microalgae-Mediated Synthesis of Gold Nanoparticles from Indonesian Chlorella vulgaris InaCC M205 with Potential Anticancer Properties for Biomedical Application.

Cell biochemistry and biophysics·2026
Same journal

Adsorption-driven Graphene Oxide SPR Biointerfaces: Coupled Thermodynamic, Kinetic, and Optical Modeling with Effective-layer Validation.

Cell biochemistry and biophysics·2026
Same journal

Identification of Ferroptosis-related Genes Associated with the Prognosis of Hepatocellular Carcinoma.

Cell biochemistry and biophysics·2026
See all related articles

Calcineurin, a key enzyme, is inhibited by two unrelated drugs, cyclosporin A and FK506. These drugs target calcineurin by binding to helper proteins, revealing conserved signaling pathways.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Immunology

Background:

  • Calcineurin is a conserved Ca(2+)-calmodulin-activated serine-threonine protein phosphatase.
  • It is a crucial enzyme in T-cell activation and microbial cation stress responses.
  • Calcineurin is the shared molecular target for structurally distinct immunosuppressive drugs: cyclosporin A and FK506.

Purpose of the Study:

  • To elucidate the mechanism of calcineurin inhibition by immunosuppressive drugs.
  • To investigate the structural basis of drug-protein-enzyme interactions.
  • To highlight the utility of yeast genetics in identifying drug targets and understanding signal transduction.

Main Methods:

  • X-ray crystallography was used to determine the structure of the FKBP12-FK506-calcineurin AB ternary complex.

Related Experiment Videos

  • Biochemical assays were employed to study inhibitor action.
  • Genetic studies in yeast were utilized to explore conserved signaling pathways.

    • Main Results:

    • The FKBP12-FK506 complex binds to a hydrophobic groove between calcineurin A and B subunits.
    • This binding mode is consistent with biochemical and genetic data on inhibitor efficacy.
    • Calcineurin's role in NF-AT regulation and microbial stress response was confirmed.

    Conclusions:

    • The structural and biochemical data provide a detailed understanding of how FK506 inhibits calcineurin.
    • Yeast genetic studies offer a powerful platform for discovering novel drug targets.
    • Conserved elements in signal transduction cascades can be elucidated through cross-species research.