1mf8
From Proteopedia
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|PDB= 1mf8 |SIZE=350|CAPTION= <scene name='initialview01'>1mf8</scene>, resolution 3.1Å | |PDB= 1mf8 |SIZE=350|CAPTION= <scene name='initialview01'>1mf8</scene>, resolution 3.1Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> | + | |LIGAND= <scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=BMT:4-METHYL-4-[(E)-2-BUTENYL]-4,N-METHYL-THREONINE'>BMT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1aui|1AUI]], [[2rma|2RMA]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mf8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mf8 OCA], [http://www.ebi.ac.uk/pdbsum/1mf8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mf8 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603288 603288]], Myotonic dystrophy, type 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=116955 116955]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Harrison, S C.]] | [[Category: Harrison, S C.]] | ||
[[Category: Jin, L.]] | [[Category: Jin, L.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: PO4]] | ||
[[Category: immunosuppressant]] | [[Category: immunosuppressant]] | ||
[[Category: protein-drug complex]] | [[Category: protein-drug complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:15:24 2008'' |
Revision as of 19:15, 30 March 2008
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| , resolution 3.1Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , , , , , | ||||||
| Activity: | Phosphoprotein phosphatase, with EC number 3.1.3.16 | ||||||
| Related: | 1AUI, 2RMA
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of human calcineurin complexed with cyclosporin A and human cyclophilin
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.
About this Structure
1MF8 is a Protein complex structure of sequences from Homo sapiens. 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
Page seeded by OCA on Sun Mar 30 22:15:24 2008
