1mf8
From Proteopedia
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Crystal Structure of human calcineurin complexed with cyclosporin A and human cyclophilin
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Cornea plana congenita, recessive OMIM:[603288], Myotonic dystrophy, type 2 OMIM:[116955]
About this Structure
1MF8 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Active as Phosphoprotein phosphatase, with EC number 3.1.3.16 Full crystallographic information is available from OCA.
Reference
Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin., Jin L, Harrison SC, Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13522-6. Epub 2002 Sep 30. PMID:12357034
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