1n8m
From Proteopedia
(New page: 200px<br /><applet load="1n8m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n8m" /> '''Solution structure of Pi4, a four disulfide ...) |
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| - | [[Image:1n8m.jpg|left|200px]]<br /><applet load="1n8m" size=" | + | [[Image:1n8m.jpg|left|200px]]<br /><applet load="1n8m" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''Solution structure of Pi4, a four disulfide bridged scorpion toxin active on potassium channels'''<br /> | '''Solution structure of Pi4, a four disulfide bridged scorpion toxin active on potassium channels'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Pi4 is a short toxin found at very low abundance in the venom of Pandinus | + | Pi4 is a short toxin found at very low abundance in the venom of Pandinus imperator scorpions. It is a potent blocker of K(+) channels. Like the other members of the alpha-KTX6 subfamily to which it belongs, it is cross-linked by four disulfide bonds. The synthetic analog (sPi4) and the natural toxin (nPi4) have been obtained by solid-phase synthesis or from scorpion venom, respectively. Analysis of two-dimensional (1)H NMR spectra of nPi4 and sPi4 indicates that both peptides have the same structure. Moreover, electrophysiological recordings of the blocking of Shaker B K(+) channels by sPi4 (K(D) = 8.5 nM) indicate that sPi4 has the same blocking activity of nPi4 (K(D) = 8.0 nM), previously described. The disulfide bonds have been independently determined by NMR and structure calculations, and by Edman-degradation/mass-spectrometry identification of peptides obtained by proteolysis of nPi4. Both approaches indicate that the pairing of the half-cystines is (6)C-(27)C, (12)C-(32)C, (16)C-(34)C, and (22)C-(37)C. The structure of the toxin has been determined by using 705 constraints derived from NMR data on sPi4. The structure, which is well defined, shows the characteristic alpha/beta scaffold of scorpion toxins. It is compared to the structure of the other alpha-KTX6 subfamily members and, in particular, to the structure of maurotoxin, which shows a different pattern of disulfide bridges despite its high degree of sequence identity (76%) with Pi4. The structure of Pi4 and the high amounts of synthetic peptide available, will enable the detailed analysis of the interaction of Pi4 with K(+) channels. |
==About this Structure== | ==About this Structure== | ||
| - | 1N8M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 1N8M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N8M OCA]. |
==Reference== | ==Reference== | ||
Solution structure of Pi4, a short four-disulfide-bridged scorpion toxin specific of potassium channels., Guijarro JI, M'Barek S, Gomez-Lagunas F, Garnier D, Rochat H, Sabatier JM, Possani L, Delepierre M, Protein Sci. 2003 Sep;12(9):1844-54. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12930984 12930984] | Solution structure of Pi4, a short four-disulfide-bridged scorpion toxin specific of potassium channels., Guijarro JI, M'Barek S, Gomez-Lagunas F, Garnier D, Rochat H, Sabatier JM, Possani L, Delepierre M, Protein Sci. 2003 Sep;12(9):1844-54. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12930984 12930984] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Barek, S | + | [[Category: Barek, S M.]] |
[[Category: Delepierre, M.]] | [[Category: Delepierre, M.]] | ||
[[Category: Garnier, D.]] | [[Category: Garnier, D.]] | ||
[[Category: Gomez-Lagunas, F.]] | [[Category: Gomez-Lagunas, F.]] | ||
| - | [[Category: Guijarro, J | + | [[Category: Guijarro, J I.]] |
[[Category: Olamendi-Portugal, T.]] | [[Category: Olamendi-Portugal, T.]] | ||
| - | [[Category: Possani, L | + | [[Category: Possani, L D.]] |
[[Category: Rochat, H.]] | [[Category: Rochat, H.]] | ||
| - | [[Category: Sabatier, J | + | [[Category: Sabatier, J M.]] |
[[Category: disulfide bridge stabilized alpha beta motif]] | [[Category: disulfide bridge stabilized alpha beta motif]] | ||
[[Category: potassium channel blocker]] | [[Category: potassium channel blocker]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:03:27 2008'' |
Revision as of 12:03, 21 February 2008
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Solution structure of Pi4, a four disulfide bridged scorpion toxin active on potassium channels
Overview
Pi4 is a short toxin found at very low abundance in the venom of Pandinus imperator scorpions. It is a potent blocker of K(+) channels. Like the other members of the alpha-KTX6 subfamily to which it belongs, it is cross-linked by four disulfide bonds. The synthetic analog (sPi4) and the natural toxin (nPi4) have been obtained by solid-phase synthesis or from scorpion venom, respectively. Analysis of two-dimensional (1)H NMR spectra of nPi4 and sPi4 indicates that both peptides have the same structure. Moreover, electrophysiological recordings of the blocking of Shaker B K(+) channels by sPi4 (K(D) = 8.5 nM) indicate that sPi4 has the same blocking activity of nPi4 (K(D) = 8.0 nM), previously described. The disulfide bonds have been independently determined by NMR and structure calculations, and by Edman-degradation/mass-spectrometry identification of peptides obtained by proteolysis of nPi4. Both approaches indicate that the pairing of the half-cystines is (6)C-(27)C, (12)C-(32)C, (16)C-(34)C, and (22)C-(37)C. The structure of the toxin has been determined by using 705 constraints derived from NMR data on sPi4. The structure, which is well defined, shows the characteristic alpha/beta scaffold of scorpion toxins. It is compared to the structure of the other alpha-KTX6 subfamily members and, in particular, to the structure of maurotoxin, which shows a different pattern of disulfide bridges despite its high degree of sequence identity (76%) with Pi4. The structure of Pi4 and the high amounts of synthetic peptide available, will enable the detailed analysis of the interaction of Pi4 with K(+) channels.
About this Structure
1N8M is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
Reference
Solution structure of Pi4, a short four-disulfide-bridged scorpion toxin specific of potassium channels., Guijarro JI, M'Barek S, Gomez-Lagunas F, Garnier D, Rochat H, Sabatier JM, Possani L, Delepierre M, Protein Sci. 2003 Sep;12(9):1844-54. PMID:12930984
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