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| + | ==PANDINUS TOXIN K-A (PITX-KA) FROM PANDINUS IMPERATOR, NMR, 20 STRUCTURES== |
| - | The line below this paragraph, containing "STRUCTURE_2pta", creates the "Structure Box" on the page.
| + | <StructureSection load='2pta' size='340' side='right'caption='[[2pta]]' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2pta]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pandinus_imperator Pandinus imperator]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PTA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PTA FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | --> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2pta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pta OCA], [https://pdbe.org/2pta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pta RCSB], [https://www.ebi.ac.uk/pdbsum/2pta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pta ProSAT]</span></td></tr> |
| - | {{STRUCTURE_2pta| PDB=2pta | SCENE= }}
| + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/KAX71_PANIM KAX71_PANIM] Potent inhibitor of the A-type voltage-gated potassium channels. Most potent inhibitor of Kv1.2/KCNA2 channels. Reversibly block the Shaker B potassium-channels (Kv1.1 sub-family).<ref>PMID:8660410</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | PiTX-K alpha, a 35-residue peptide recently isolated from the venom of Pandinus imperator, blocks the rapidly inactivating (A-type) K+ channel(s) in rat brain synaptosomes and the cloned Kv 1.2 potassium channel at very low toxin concentrations (6 nM and 32 pM, respectively) [Rogowski, R. S., Collins, J. H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A., Tenenholz, T. C., Weber, D. J., & Blaustein, M. P. (1996) Mol. Pharmacol. 50, 1167-1177]. The three-dimensional structure of PiTX-K alpha was determined using NMR spectroscopy in order to understand its selectivity and affinity toward K+ channels. PiTX-K alpha was found to have an alpha-helix from residues 10 to 21 and two beta-strands (betaI, 26-28; betaII, 33-35) connected by a type II beta-turn to form a small antiparallel beta-sheet. Three disulfide bonds, which are conserved in all members of the charybdotoxin family (alpha-K toxins), anchor one face of the alpha-helix to the beta-sheet. The N-terminal portion of PiTX-K alpha has three fewer residues than other alpha-K toxins such as charybdotoxin. Rather than forming a third beta-strand as found for other alpha-K toxins, the N-terminal region of PiTX-K alpha adopts an extended conformation. This structural difference in PiTX-K alpha together with differences in sequence at Pro-10, Tyr-14, and Asn-25 (versus Ser-10, Trp-14, and Arg-25 in CTX) may explain why PiTX-K alpha does not block maxi-K+ channels. Differences in three-dimensional structure between PiTX-K alpha and charybdotoxin are also observed in both the tight turn and the loop that connects the first beta-strand to the alpha-helix. As a result, side chains of two residues (Tyr-23 and Arg-31) are in regions of PiTX-K alpha that probably interact with rapidly inactivating A-type K+ channels. The analogous residues in charybdotoxin are positioned differently on the toxin surface. Thus, the locations of Tyr-23 and Arg-31 side chains in PiTX-K alpha could explain why this toxin blocks A-type channels at much lower concentrations than does charybdotoxin. |
| | | | |
| - | '''PANDINUS TOXIN K-A (PITX-KA) FROM PANDINUS IMPERATOR, NMR, 20 STRUCTURES'''
| + | Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels.,Tenenholz TC, Rogowski RS, Collins JH, Blaustein MP, Weber DJ Biochemistry. 1997 Mar 11;36(10):2763-71. PMID:9062103<ref>PMID:9062103</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | PiTX-K alpha, a 35-residue peptide recently isolated from the venom of Pandinus imperator, blocks the rapidly inactivating (A-type) K+ channel(s) in rat brain synaptosomes and the cloned Kv 1.2 potassium channel at very low toxin concentrations (6 nM and 32 pM, respectively) [Rogowski, R. S., Collins, J. H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A., Tenenholz, T. C., Weber, D. J., & Blaustein, M. P. (1996) Mol. Pharmacol. 50, 1167-1177]. The three-dimensional structure of PiTX-K alpha was determined using NMR spectroscopy in order to understand its selectivity and affinity toward K+ channels. PiTX-K alpha was found to have an alpha-helix from residues 10 to 21 and two beta-strands (betaI, 26-28; betaII, 33-35) connected by a type II beta-turn to form a small antiparallel beta-sheet. Three disulfide bonds, which are conserved in all members of the charybdotoxin family (alpha-K toxins), anchor one face of the alpha-helix to the beta-sheet. The N-terminal portion of PiTX-K alpha has three fewer residues than other alpha-K toxins such as charybdotoxin. Rather than forming a third beta-strand as found for other alpha-K toxins, the N-terminal region of PiTX-K alpha adopts an extended conformation. This structural difference in PiTX-K alpha together with differences in sequence at Pro-10, Tyr-14, and Asn-25 (versus Ser-10, Trp-14, and Arg-25 in CTX) may explain why PiTX-K alpha does not block maxi-K+ channels. Differences in three-dimensional structure between PiTX-K alpha and charybdotoxin are also observed in both the tight turn and the loop that connects the first beta-strand to the alpha-helix. As a result, side chains of two residues (Tyr-23 and Arg-31) are in regions of PiTX-K alpha that probably interact with rapidly inactivating A-type K+ channels. The analogous residues in charybdotoxin are positioned differently on the toxin surface. Thus, the locations of Tyr-23 and Arg-31 side chains in PiTX-K alpha could explain why this toxin blocks A-type channels at much lower concentrations than does charybdotoxin. | + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 2PTA is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pandinus_imperator Pandinus imperator]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PTA OCA].
| + | </div> |
| | + | <div class="pdbe-citations 2pta" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels., Tenenholz TC, Rogowski RS, Collins JH, Blaustein MP, Weber DJ, Biochemistry. 1997 Mar 11;36(10):2763-71. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9062103 9062103]
| + | *[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Pandinus imperator]] | | [[Category: Pandinus imperator]] |
| - | [[Category: Single protein]]
| + | [[Category: Blaustein MP]] |
| - | [[Category: Blaustein, M P.]] | + | [[Category: Collins JH]] |
| - | [[Category: Collins, J H.]] | + | [[Category: Rogowski RS]] |
| - | [[Category: Rogowski, R S.]] | + | [[Category: Tenenholz TC]] |
| - | [[Category: Tenenholz, T C.]] | + | [[Category: Weber DJ]] |
| - | [[Category: Weber, D J.]] | + | |
| - | [[Category: Alpha-k toxin family]]
| + | |
| - | [[Category: Neurotoxin]]
| + | |
| - | [[Category: Nmr solution structure]]
| + | |
| - | [[Category: Potassium channel blocker]]
| + | |
| - | [[Category: Scorpion toxin]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 13:46:22 2008''
| + | |
| Structural highlights
Function
KAX71_PANIM Potent inhibitor of the A-type voltage-gated potassium channels. Most potent inhibitor of Kv1.2/KCNA2 channels. Reversibly block the Shaker B potassium-channels (Kv1.1 sub-family).[1]
Publication Abstract from PubMed
PiTX-K alpha, a 35-residue peptide recently isolated from the venom of Pandinus imperator, blocks the rapidly inactivating (A-type) K+ channel(s) in rat brain synaptosomes and the cloned Kv 1.2 potassium channel at very low toxin concentrations (6 nM and 32 pM, respectively) [Rogowski, R. S., Collins, J. H., O'Neil, T. J., Gustafson, T. A., Werkman, T. A., Rogawski, M. A., Tenenholz, T. C., Weber, D. J., & Blaustein, M. P. (1996) Mol. Pharmacol. 50, 1167-1177]. The three-dimensional structure of PiTX-K alpha was determined using NMR spectroscopy in order to understand its selectivity and affinity toward K+ channels. PiTX-K alpha was found to have an alpha-helix from residues 10 to 21 and two beta-strands (betaI, 26-28; betaII, 33-35) connected by a type II beta-turn to form a small antiparallel beta-sheet. Three disulfide bonds, which are conserved in all members of the charybdotoxin family (alpha-K toxins), anchor one face of the alpha-helix to the beta-sheet. The N-terminal portion of PiTX-K alpha has three fewer residues than other alpha-K toxins such as charybdotoxin. Rather than forming a third beta-strand as found for other alpha-K toxins, the N-terminal region of PiTX-K alpha adopts an extended conformation. This structural difference in PiTX-K alpha together with differences in sequence at Pro-10, Tyr-14, and Asn-25 (versus Ser-10, Trp-14, and Arg-25 in CTX) may explain why PiTX-K alpha does not block maxi-K+ channels. Differences in three-dimensional structure between PiTX-K alpha and charybdotoxin are also observed in both the tight turn and the loop that connects the first beta-strand to the alpha-helix. As a result, side chains of two residues (Tyr-23 and Arg-31) are in regions of PiTX-K alpha that probably interact with rapidly inactivating A-type K+ channels. The analogous residues in charybdotoxin are positioned differently on the toxin surface. Thus, the locations of Tyr-23 and Arg-31 side chains in PiTX-K alpha could explain why this toxin blocks A-type channels at much lower concentrations than does charybdotoxin.
Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels.,Tenenholz TC, Rogowski RS, Collins JH, Blaustein MP, Weber DJ Biochemistry. 1997 Mar 11;36(10):2763-71. PMID:9062103[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gomez-Lagunas F, Olamendi-Portugal T, Zamudio FZ, Possani LD. Two novel toxins from the venom of the scorpion Pandinus imperator show that the N-terminal amino acid sequence is important for their affinities towards Shaker B K+ channels. J Membr Biol. 1996 Jul;152(1):49-56. PMID:8660410
- ↑ Tenenholz TC, Rogowski RS, Collins JH, Blaustein MP, Weber DJ. Solution structure for Pandinus toxin K-alpha (PiTX-K alpha), a selective blocker of A-type potassium channels. Biochemistry. 1997 Mar 11;36(10):2763-71. PMID:9062103 doi:10.1021/bi9628432
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