1aui
From Proteopedia
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|PDB= 1aui |SIZE=350|CAPTION= <scene name='initialview01'>1aui</scene>, resolution 2.1Å | |PDB= 1aui |SIZE=350|CAPTION= <scene name='initialview01'>1aui</scene>, resolution 2.1Å | ||
|SITE= <scene name='pdbsite=CA1:Ca+Binding+Site'>CA1</scene>, <scene name='pdbsite=CA2:Ca+Binding+Site'>CA2</scene>, <scene name='pdbsite=CA3:Ca+Binding+Site'>CA3</scene>, <scene name='pdbsite=CA4:Ca+Binding+Site'>CA4</scene>, <scene name='pdbsite=FEB:Fe+Binding+Site'>FEB</scene> and <scene name='pdbsite=ZNB:Zn+Binding+Site'>ZNB</scene> | |SITE= <scene name='pdbsite=CA1:Ca+Binding+Site'>CA1</scene>, <scene name='pdbsite=CA2:Ca+Binding+Site'>CA2</scene>, <scene name='pdbsite=CA3:Ca+Binding+Site'>CA3</scene>, <scene name='pdbsite=CA4:Ca+Binding+Site'>CA4</scene>, <scene name='pdbsite=FEB:Fe+Binding+Site'>FEB</scene> and <scene name='pdbsite=ZNB:Zn+Binding+Site'>ZNB</scene> | ||
| - | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1aui FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1aui OCA], [http://www.ebi.ac.uk/pdbsum/1aui PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1aui RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Calcineurin (CaN) is a calcium- and calmodulin-dependent protein serine/threonine phosphate which is critical for several important cellular processes, including T-cell activation. CaN is the target of the immunosuppressive drugs cyclosporin A and FK506, which inhibit CaN after forming complexes with cytoplasmic binding proteins (cyclophilin and FKBP12, respectively). We report here the crystal structures of full-length human CaN at 2.1 A resolution and of the complex of human CaN with FKBP12-FK506 at 3.5 A resolution. In the native CaN structure, an auto-inhibitory element binds at the Zn/Fe-containing active site. The metal-site geometry and active-site water structure suggest a catalytic mechanism involving nucleophilic attack on the substrate phosphate by a metal-activated water molecule. In the FKBP12-FK506-CaN complex, the auto-inhibitory element is displaced from the active site. The site of binding of FKBP12-FK506 appears to be shared by other non-competitive inhibitors of calcineurin, including a natural anchoring protein. | Calcineurin (CaN) is a calcium- and calmodulin-dependent protein serine/threonine phosphate which is critical for several important cellular processes, including T-cell activation. CaN is the target of the immunosuppressive drugs cyclosporin A and FK506, which inhibit CaN after forming complexes with cytoplasmic binding proteins (cyclophilin and FKBP12, respectively). We report here the crystal structures of full-length human CaN at 2.1 A resolution and of the complex of human CaN with FKBP12-FK506 at 3.5 A resolution. In the native CaN structure, an auto-inhibitory element binds at the Zn/Fe-containing active site. The metal-site geometry and active-site water structure suggest a catalytic mechanism involving nucleophilic attack on the substrate phosphate by a metal-activated water molecule. In the FKBP12-FK506-CaN complex, the auto-inhibitory element is displaced from the active site. The site of binding of FKBP12-FK506 appears to be shared by other non-competitive inhibitors of calcineurin, including a natural anchoring protein. | ||
| - | |||
| - | ==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: Tempczyk, A.]] | [[Category: Tempczyk, A.]] | ||
[[Category: Villafranca, J E.]] | [[Category: Villafranca, J E.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: FE]] | ||
| - | [[Category: ZN]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
[[Category: immunosuppression]] | [[Category: immunosuppression]] | ||
[[Category: phosphatase]] | [[Category: phosphatase]] | ||
| - | ''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 18:47:50 2008'' |
Revision as of 15:47, 30 March 2008
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| , resolution 2.1Å | |||||||
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| Sites: | , , , , and | ||||||
| Ligands: | , , | ||||||
| Activity: | Phosphoprotein phosphatase, with EC number 3.1.3.16 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HUMAN CALCINEURIN HETERODIMER
Overview
Calcineurin (CaN) is a calcium- and calmodulin-dependent protein serine/threonine phosphate which is critical for several important cellular processes, including T-cell activation. CaN is the target of the immunosuppressive drugs cyclosporin A and FK506, which inhibit CaN after forming complexes with cytoplasmic binding proteins (cyclophilin and FKBP12, respectively). We report here the crystal structures of full-length human CaN at 2.1 A resolution and of the complex of human CaN with FKBP12-FK506 at 3.5 A resolution. In the native CaN structure, an auto-inhibitory element binds at the Zn/Fe-containing active site. The metal-site geometry and active-site water structure suggest a catalytic mechanism involving nucleophilic attack on the substrate phosphate by a metal-activated water molecule. In the FKBP12-FK506-CaN complex, the auto-inhibitory element is displaced from the active site. The site of binding of FKBP12-FK506 appears to be shared by other non-competitive inhibitors of calcineurin, including a natural anchoring protein.
About this Structure
1AUI is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex., Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW, et al., Nature. 1995 Dec 7;378(6557):641-4. PMID:8524402
Page seeded by OCA on Sun Mar 30 18:47:50 2008
