1MF8

Crystal Structure of human calcineurin complexed with cyclosporin A and human cyclophilin

Summary for 1MF8

• Entry DOI: 10.2210/pdb1mf8/pdb
• Related: 1AUI 1BCK 1C5F 1CSA 1CWA 1CWB 1CWC 1CWF 1CWH 1CWI 1CWJ 1CWK 1CWL 1CWM 1CWO 1CYA 1CYB 1CYN 1IKF 1M63 1MIK 1QNG 1QNH 1XQ7 2ESL 2OJU 2POY 2RMA 2RMB 2RMC 2WFJ 2X2C 2X7K 2Z6W 3BO7 3CYS 3EOV
• Related PRD ID: PRD_000142
• Descriptor: CALMODULIN-DEPENDENT CALCINEURIN A SUBUNIT, ALPHA ISOFORM, CALCINEURIN B SUBUNIT ISOFORM 1, PEPTIDYL-PROLYL CIS-TRANS ISOMERASE A, ... (6 entities in total)
• Functional Keywords: hydrolase-isomerase-immunosuppressant complex, calcineurin-cyclophilin-cyclosporin complex, cyclosporin a, immunosuppressant, hydrolase, isomerase, hydrolase/isomerase/immunosuppressant
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus (By similarity): Q08209; Cytoplasm: P62937
• Total number of polymer chains: 4
• Total formula weight: 81605.95

Authors

Jin, L.,Harrison, S.C. (deposition date: 2002-08-09, release date: 2002-10-16, Last modification date: 2025-03-26)

Primary citation

Jin, L.,Harrison, S.C.
Crystal Structure of Human Calcineurin Complexed with Cyclosporin a and Human Cyclophilin
Proc.Natl.Acad.Sci.USA, 99:13522-, 2002

PubMed Abstract: Calcineurin (Cn), a Ca(2+)/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 A. 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.

PubMed: 12357034
DOI: 10.1073/PNAS.212504399

Experimental method

X-RAY DIFFRACTION (3.1 Å)