Nature Communications (Sep 2019)
Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents
- Praveen R. Juvvadi,
- David Fox,
- Benjamin G. Bobay,
- Michael J. Hoy,
- Sophie M. C. Gobeil,
- Ronald A. Venters,
- Zanetta Chang,
- Jackie J. Lin,
- Anna Floyd Averette,
- D. Christopher Cole,
- Blake C. Barrington,
- Joshua D. Wheaton,
- Maria Ciofani,
- Michael Trzoss,
- Xiaoming Li,
- Soo Chan Lee,
- Ying-Lien Chen,
- Mitchell Mutz,
- Leonard D. Spicer,
- Maria A. Schumacher,
- Joseph Heitman,
- William J. Steinbach
Affiliations
- Praveen R. Juvvadi
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center
- David Fox
- Beryllium Discovery Corp.
- Benjamin G. Bobay
- Duke University NMR Center, Duke University Medical Center
- Michael J. Hoy
- Department of Molecular Genetics and Microbiology, Duke University Medical Center
- Sophie M. C. Gobeil
- Department of Biochemistry, Duke University
- Ronald A. Venters
- Duke University NMR Center, Duke University Medical Center
- Zanetta Chang
- Department of Molecular Genetics and Microbiology, Duke University Medical Center
- Jackie J. Lin
- Department of Molecular Genetics and Microbiology, Duke University Medical Center
- Anna Floyd Averette
- Department of Molecular Genetics and Microbiology, Duke University Medical Center
- D. Christopher Cole
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center
- Blake C. Barrington
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center
- Joshua D. Wheaton
- Department of Immunology, Duke University Medical Center
- Maria Ciofani
- Department of Immunology, Duke University Medical Center
- Michael Trzoss
- Amplyx Pharmaceuticals
- Xiaoming Li
- Amplyx Pharmaceuticals
- Soo Chan Lee
- South Texas Center for Emerging Infectious Diseases, Department of Biology, The University of Texas at San Antonio
- Ying-Lien Chen
- Department of Plant Pathology and Microbiology, National Taiwan University
- Mitchell Mutz
- Amplyx Pharmaceuticals
- Leonard D. Spicer
- Duke University NMR Center, Duke University Medical Center
- Maria A. Schumacher
- Department of Biochemistry, Duke University
- Joseph Heitman
- Department of Molecular Genetics and Microbiology, Duke University Medical Center
- William J. Steinbach
- Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center
- DOI
- https://doi.org/10.1038/s41467-019-12199-1
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 18
Abstract
FK506 is a potential antifungal compound that inhibits calcineurin, but it also has immunosuppressive activity. Here, Juvvadi et al. report the structure of FK506 in complex with the FK506-binding protein FKPB12 and calcineurin, and design a less immunosuppresive FK506 analog with antifungal activity in mice.
