Crystal structure of human calcineurin complexed with cyclosporin a and human cyclophilin
View/ Open
Author
Jin, Lei
Harrison, Stephen C.
Published Version
https://doi.org/10.1073/pnas.212504399Metadata
Show full item recordCitation
Jin, L., and S. C. Harrison. 2002. “Crystal Structure of Human Calcineurin Complexed with Cyclosporin A and Human Cyclophilin.” Proceedings of the National Academy of Sciences 99 (21): 13522–26. doi:10.1073/pnas.212504399.Abstract
Calcineurin (Cn), a Ca2+/calmodulin-dependent Ser/Thr protein phosphatase, is an important participant in signaling pathways that activate T cells. It is the target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. These drugs bind proteins known as cyclophilin (Cyp) and FK506-binding protein, respectively, and the drug-protein complexes in turn inhibit Cn. We report the crystal structure of a Cyp/CsA/Cn ternary complex, determined to a resolution of 3.1 Angstrom. Residues 3-9 of CsA, particularly N-methyl leucines 4 and 6, and Trp-121 of Cyp form a composite surface for interaction with Cn. The hydrophobic interface buries two hydrogen bonds. The structure accounts clearly for the effects of mutations in Cn on CsA-resistance and for the way modifications of CsA alter immunosuppressive activity.Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41542828
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)