1aui
From Proteopedia
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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 ... | + | 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== | ==About this Structure== | ||
| - | 1AUI is a | + | 1AUI is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA, ZN and FE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Structure known Active Sites: CA1, CA2, CA3, CA4, FEB and ZNB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1AUI OCA]. |
==Reference== | ==Reference== | ||
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[[Category: phosphatase]] | [[Category: phosphatase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 14:58:51 2007'' |
Revision as of 12:53, 5 November 2007
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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 with CA, ZN and FE as ligands. Active as Phosphoprotein phosphatase, with EC number 3.1.3.16 Structure known Active Sites: CA1, CA2, CA3, CA4, FEB and ZNB. 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
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