1bei
From Proteopedia
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| - | [[Image:1bei.gif|left|200px]] | + | [[Image:1bei.gif|left|200px]] |
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| - | '''SHK-DNP22: A POTENT KV1.3-SPECIFIC IMMUNOSUPPRESSIVE POLYPEPTIDE, NMR, 20 STRUCTURES''' | + | {{Structure |
| + | |PDB= 1bei |SIZE=350|CAPTION= <scene name='initialview01'>1bei</scene> | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= | ||
| + | }} | ||
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| + | '''SHK-DNP22: A POTENT KV1.3-SPECIFIC IMMUNOSUPPRESSIVE POLYPEPTIDE, NMR, 20 STRUCTURES''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1BEI is a [ | + | 1BEI is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Stichodactyla_helianthus Stichodactyla helianthus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BEI OCA]. |
==Reference== | ==Reference== | ||
| - | ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide., Kalman K, Pennington MW, Lanigan MD, Nguyen A, Rauer H, Mahnir V, Paschetto K, Kem WR, Grissmer S, Gutman GA, Christian EP, Cahalan MD, Norton RS, Chandy KG, J Biol Chem. 1998 Dec 4;273(49):32697-707. PMID:[http:// | + | ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide., Kalman K, Pennington MW, Lanigan MD, Nguyen A, Rauer H, Mahnir V, Paschetto K, Kem WR, Grissmer S, Gutman GA, Christian EP, Cahalan MD, Norton RS, Chandy KG, J Biol Chem. 1998 Dec 4;273(49):32697-707. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9830012 9830012] |
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Stichodactyla helianthus]] | [[Category: Stichodactyla helianthus]] | ||
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[[Category: sea anemone]] | [[Category: sea anemone]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:09:58 2008'' |
Revision as of 08:10, 20 March 2008
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SHK-DNP22: A POTENT KV1.3-SPECIFIC IMMUNOSUPPRESSIVE POLYPEPTIDE, NMR, 20 STRUCTURES
Overview
The voltage-gated potassium channel in T lymphocytes, Kv1.3, is an important molecular target for immunosuppressive agents. A structurally defined polypeptide, ShK, from the sea anemone Stichodactyla helianthus inhibited Kv1.3 potently and also blocked Kv1.1, Kv1.4, and Kv1.6 at subnanomolar concentrations. Using mutant cycle analysis in conjunction with complementary mutagenesis of ShK and Kv1.3, and utilizing the structure of ShK, we determined a likely docking configuration for this peptide in the channel. Based upon this topological information, we replaced the critical Lys22 in ShK with the positively charged, non-natural amino acid diaminopropionic acid (ShK-Dap22) and generated a highly selective and potent blocker of the T-lymphocyte channel. ShK-Dap22, at subnanomolar concentrations, suppressed anti-CD3 induced human T-lymphocyte [3H]thymidine incorporation in vitro. Toxicity with this mutant peptide was low in a rodent model, with a median paralytic dose of approximately 200 mg/kg body weight following intravenous administration. The overall structure of ShK-Dap22 in solution, as determined from NMR data, is similar to that of native ShK toxin, but there are some differences in the residues involved in potassium channel binding. Based on these results, we propose that ShK-Dap22 or a structural analogue may have use as an immunosuppressant for the prevention of graft rejection and for the treatment of autoimmune diseases.
About this Structure
1BEI is a Single protein structure of sequence from Stichodactyla helianthus. Full crystallographic information is available from OCA.
Reference
ShK-Dap22, a potent Kv1.3-specific immunosuppressive polypeptide., Kalman K, Pennington MW, Lanigan MD, Nguyen A, Rauer H, Mahnir V, Paschetto K, Kem WR, Grissmer S, Gutman GA, Christian EP, Cahalan MD, Norton RS, Chandy KG, J Biol Chem. 1998 Dec 4;273(49):32697-707. PMID:9830012
Page seeded by OCA on Thu Mar 20 10:09:58 2008
Categories: Single protein | Stichodactyla helianthus | Cahalan, M D. | Chandy, K G. | Christian, E P. | Grissmer, S. | Gutman, G A. | Kalman, K. | Kem, W R. | Lanigan, M D. | Mahnir, V. | Nguyen, A. | Norton, R S. | Paschetto, K. | Pennington, M W. | Rauer, H. | Immunosuppressant neurotoxin | Potassium channel inhibitor | Sea anemone
