dc.contributor.author | Jin, Lei | |
dc.contributor.author | Harrison, Stephen C. | |
dc.date.accessioned | 2019-10-13T16:04:00Z | |
dc.date.issued | 2002 | |
dc.identifier.citation | 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. | |
dc.identifier.issn | 0027-8424 | |
dc.identifier.issn | 0744-2831 | |
dc.identifier.issn | 1091-6490 | |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:41542828 | * |
dc.description.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. | |
dc.language.iso | en_US | |
dc.publisher | National Academy of Sciences | |
dash.license | LAA | |
dc.title | Crystal structure of human calcineurin complexed with cyclosporin a and human cyclophilin | |
dc.type | Journal Article | |
dc.description.version | Version of Record | |
dc.relation.journal | Proceedings of the National Academy of Sciences of the United States of America | |
dash.depositing.author | Harrison, Stephen::29356e859c6d3698df98e8184352069e::600 | |
dc.date.available | 2019-10-13T16:04:00Z | |
dash.workflow.comments | 1Science Serial ID 89383 | |
dc.identifier.doi | 10.1073/pnas.212504399 | |
dash.source.volume | 99;21 | |
dash.source.page | 13522 | |