Vm24 Scorpion Toxin
From Proteopedia
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Positions <scene name='84/842913/Resi_7-9/1'>7-9</scene> and <scene name='84/842913/Resi_17-20/1'>17-20</scene> are not well defined because they have a reduced number of Nuclear Overhauser effects NOEs [https://pubmed-ncbi-nlm-nih-gov.ezproxy.uvm.edu/22540187/?from_single_result=Structure%2C+function%2C+and+chemical+synthesis+of+Vaejovis+mexicanus+peptide+24%3A+a+novel+potent+blocker+of+Kv1.3+potassium+channels+of+human+T+lymphocytes.&expanded_search_query=Structure%2C+function%2C+and+chemical+synthesis+of+Vaejovis+mexicanus+peptide+24%3A+a+novel+potent+blocker+of+Kv1.3+potassium+channels+of+human+T+lymphocytes.] All <scene name='84/842913/All_disulfides/2'>cysteines</scene> and <scene name='84/842913/Ile4/1'>Ile4</scene> are buried entirely, but all other residues are exposed. <scene name='84/842913/Tyr35/1'>Tyr35</scene> and <scene name='84/842913/Cys36/1'>Cys36</scene> are in a very flexible region, which is interesting because they are adjacent to a <scene name='84/842913/Ssbonds_21-36/1'>disulfide bridge</scene>. | Positions <scene name='84/842913/Resi_7-9/1'>7-9</scene> and <scene name='84/842913/Resi_17-20/1'>17-20</scene> are not well defined because they have a reduced number of Nuclear Overhauser effects NOEs [https://pubmed-ncbi-nlm-nih-gov.ezproxy.uvm.edu/22540187/?from_single_result=Structure%2C+function%2C+and+chemical+synthesis+of+Vaejovis+mexicanus+peptide+24%3A+a+novel+potent+blocker+of+Kv1.3+potassium+channels+of+human+T+lymphocytes.&expanded_search_query=Structure%2C+function%2C+and+chemical+synthesis+of+Vaejovis+mexicanus+peptide+24%3A+a+novel+potent+blocker+of+Kv1.3+potassium+channels+of+human+T+lymphocytes.] All <scene name='84/842913/All_disulfides/2'>cysteines</scene> and <scene name='84/842913/Ile4/1'>Ile4</scene> are buried entirely, but all other residues are exposed. <scene name='84/842913/Tyr35/1'>Tyr35</scene> and <scene name='84/842913/Cys36/1'>Cys36</scene> are in a very flexible region, which is interesting because they are adjacent to a <scene name='84/842913/Ssbonds_21-36/1'>disulfide bridge</scene>. | ||
==Function== | ==Function== | ||
- | Vm24 is a potent and selective inhibitor of Kv1.3 potassium channels of human T lymphocytes. In vitro, Kv1.3 current is reduced by approximately 2/3 <sub>rds in the presence of 3pM of Vm24 | + | Vm24 is a potent and selective inhibitor of Kv1.3 potassium channels of human T lymphocytes. In vitro, Kv1.3 current is reduced by approximately 2/3 <sub>rds</sub> in the presence of 3pM of Vm24 |
Revision as of 16:42, 26 April 2020
Contents |
Introduction
Vm24 synthetic scorpion toxin is a peptide toxin isolated from Vaejovis mexicanus scorpion venom. It is a potent inhibitor of Kv1.3 potassium channels of human T lymphocytes. Its high affinity and specificity for human lymphocytes makes it a candidate for the treatment of several autoimmune disorders.

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Protein Source
Gurolla G.B et al [1] isolated the peptide components of Vaejovis mexicanus smithi venom using high-performance liquid chromatography. Over 200 components were identified. The structure of Vm24 was determined by solution NMR spectroscopy, and it was sequenced via trypsin digestion. The a synthetic Vm24 gene was created and artificially translated to produce the synthetic Vm24 toxin displayed.
General Structure
Vm24 is a single chain protein consisting of 36 amino acids. It has a molecular weight of 3,873 daltons. It consists of a three strand (S1,S2,S3) anti-parallel and one single turn with holding the chain together. The disulfides exist between , , , and . The disulfide bonds between and with the C-terminal strand of the β-sheet. The disulfide bridge between connects the The abundant disulfides in this protein are highly important in conferring it's unusual, strained conformation [2]. Positions and are not well defined because they have a reduced number of Nuclear Overhauser effects NOEs [3] All and are buried entirely, but all other residues are exposed. and are in a very flexible region, which is interesting because they are adjacent to a .
Function
Vm24 is a potent and selective inhibitor of Kv1.3 potassium channels of human T lymphocytes. In vitro, Kv1.3 current is reduced by approximately 2/3 rds in the presence of 3pM of Vm24