This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

1hp2

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.

Structural highlights

1hp2 is a 1 chain structure with sequence from Tityus serrulatus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAX41_TITSE Potently blocks Kv1.1/KCNA1 (85%), Kv1.2/KCNA2 (91%), Kv1.3/KCNA3 (89%), Kv1.6/KCNA6 (94%), and Shaker (97%).^[1] ^[2] ^[3]

Publication Abstract from PubMed

A toxin from the scorpion Tityus serrulatus (TsTX-Kalpha) blocks native squid K(+) channels and their cloned counterpart, sqKv1A, at pH 8 ((native)K(d) approximately 20 nM; (sqKv1A)K(d) approximately 10 nM). In both cases, decreasing the pH below 7.0 significantly diminishes the TsTX-Kalpha effect (pK = 6.6). In the cloned squid channel, the pH dependence of the block is abolished by a single point mutation (H351G), and no change in toxin affinity was observed at higher pH values (pH > or =8.0). To further investigate the TsTX-Kalpha-sqKv1A interaction, the three-dimensional structure of TsTX-Kalpha was determined in solution by NMR spectroscopy, and a model of the TsTX-Kalpha-sqKv1A complex was generated. As found for other alpha-K toxins such as charybdotoxin (CTX), site-directed mutagenesis at toxin residue K27 (K27A, K27R, and K27E) significantly reduced the toxin's affinity for sqKv1A channels. This is consistent with the TsTX-Kalpha-sqKv1A model reported here, which has K27 of the toxin inserted into the ion conduction pathway of the K(+) channel. This toxin-channel model also illustrates a possible mechanism for the pH-dependent block whereby lysine residues from TsTX-Kalpha (K6 and K23) are repelled by protonated H351 on sqKv1A at low pH.

Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A).,Ellis KC, Tenenholz TC, Jerng H, Hayhurst M, Dudlak CS, Gilly WF, Blaustein MP, Weber DJ Biochemistry. 2001 May 22;40(20):5942-53. PMID:11352729^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rodrigues AR, Arantes EC, Monje F, Stuhmer W, Varanda WA. Tityustoxin-K(alpha) blockade of the voltage-gated potassium channel Kv1.3. Br J Pharmacol. 2003 Jul;139(6):1180-6. PMID:12871837 doi:http://dx.doi.org/10.1038/sj.bjp.0705343
↑ Cerni FA, Pucca MB, Peigneur S, Cremonez CM, Bordon KC, Tytgat J, Arantes EC. Electrophysiological characterization of Ts6 and Ts7, K(+) channel toxins isolated through an improved Tityus serrulatus venom purification procedure. Toxins (Basel). 2014 Feb 28;6(3):892-913. doi: 10.3390/toxins6030892. PMID:24590385 doi:http://dx.doi.org/10.3390/toxins6030892
↑ Rogowski RS, Krueger BK, Collins JH, Blaustein MP. Tityustoxin K alpha blocks voltage-gated noninactivating K+ channels and unblocks inactivating K+ channels blocked by alpha-dendrotoxin in synaptosomes. Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1475-9. PMID:7509073
↑ Ellis KC, Tenenholz TC, Jerng H, Hayhurst M, Dudlak CS, Gilly WF, Blaustein MP, Weber DJ. Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A). Biochemistry. 2001 May 22;40(20):5942-53. PMID:11352729

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1hp2"

@@ Line 1: / Line 1: @@
-[[Image:1hp2.jpg|left|200px]]<br /><applet load="1hp2" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1hp2" />
-'''SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.'''<br />
-==Overview==
+==SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.==
-A toxin from the scorpion Tityus serrulatus (TsTX-Kalpha) blocks native, squid K(+) channels and their cloned counterpart, sqKv1A, at pH 8, ((native)K(d) approximately 20 nM; (sqKv1A)K(d) approximately 10 nM). In, both cases, decreasing the pH below 7.0 significantly diminishes the, TsTX-Kalpha effect (pK = 6.6). In the cloned squid channel, the pH, dependence of the block is abolished by a single point mutation (H351G), and no change in toxin affinity was observed at higher pH values (pH &gt; or, =8.0). To further investigate the TsTX-Kalpha-sqKv1A interaction, the, three-dimensional structure of TsTX-Kalpha was determined in solution by, NMR spectroscopy, and a model of the TsTX-Kalpha-sqKv1A complex was, generated. As found for other alpha-K toxins such as charybdotoxin (CTX), site-directed mutagenesis at toxin residue K27 (K27A, K27R, and K27E), significantly reduced the toxin's affinity for sqKv1A channels. This is, consistent with the TsTX-Kalpha-sqKv1A model reported here, which has K27, of the toxin inserted into the ion conduction pathway of the K(+) channel., This toxin-channel model also illustrates a possible mechanism for the, pH-dependent block whereby lysine residues from TsTX-Kalpha (K6 and K23), are repelled by protonated H351 on sqKv1A at low pH.
+<StructureSection load='1hp2' size='340' side='right'caption='[[1hp2]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1hp2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tityus_serrulatus Tityus serrulatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HP2 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1hp2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hp2 OCA], [https://pdbe.org/1hp2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hp2 RCSB], [https://www.ebi.ac.uk/pdbsum/1hp2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hp2 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/KAX41_TITSE KAX41_TITSE] Potently blocks Kv1.1/KCNA1 (85%), Kv1.2/KCNA2 (91%), Kv1.3/KCNA3 (89%), Kv1.6/KCNA6 (94%), and Shaker (97%).<ref>PMID:12871837</ref> <ref>PMID:24590385</ref> <ref>PMID:7509073</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+A toxin from the scorpion Tityus serrulatus (TsTX-Kalpha) blocks native squid K(+) channels and their cloned counterpart, sqKv1A, at pH 8 ((native)K(d) approximately 20 nM; (sqKv1A)K(d) approximately 10 nM). In both cases, decreasing the pH below 7.0 significantly diminishes the TsTX-Kalpha effect (pK = 6.6). In the cloned squid channel, the pH dependence of the block is abolished by a single point mutation (H351G), and no change in toxin affinity was observed at higher pH values (pH &gt; or =8.0). To further investigate the TsTX-Kalpha-sqKv1A interaction, the three-dimensional structure of TsTX-Kalpha was determined in solution by NMR spectroscopy, and a model of the TsTX-Kalpha-sqKv1A complex was generated. As found for other alpha-K toxins such as charybdotoxin (CTX), site-directed mutagenesis at toxin residue K27 (K27A, K27R, and K27E) significantly reduced the toxin's affinity for sqKv1A channels. This is consistent with the TsTX-Kalpha-sqKv1A model reported here, which has K27 of the toxin inserted into the ion conduction pathway of the K(+) channel. This toxin-channel model also illustrates a possible mechanism for the pH-dependent block whereby lysine residues from TsTX-Kalpha (K6 and K23) are repelled by protonated H351 on sqKv1A at low pH.
-==About this Structure==
+Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A).,Ellis KC, Tenenholz TC, Jerng H, Hayhurst M, Dudlak CS, Gilly WF, Blaustein MP, Weber DJ Biochemistry. 2001 May 22;40(20):5942-53. PMID:11352729<ref>PMID:11352729</ref>
-HP2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Tityus_serrulatus Tityus serrulatus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HP2 OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Interaction of a toxin from the scorpion Tityus serrulatus with a cloned K+ channel from squid (sqKv1A)., Ellis KC, Tenenholz TC, Jerng H, Hayhurst M, Dudlak CS, Gilly WF, Blaustein MP, Weber DJ, Biochemistry. 2001 May 22;40(20):5942-53. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11352729 11352729]
+</div>
-[[Category: Single protein]]
+<div class="pdbe-citations 1hp2" style="background-color:#fffaf0;"></div>
-[[Category: Tityus serrulatus]]
-[[Category: Blaustein, M.P.]]
-[[Category: Ellis, K.C.]]
-[[Category: Gilly, W.F.]]
-[[Category: Tenenholz, T.C.]]
-[[Category: Weber, D.J.]]
-[[Category: alpha-k toxin]]
-[[Category: k+ channel]]
-[[Category: scorpion toxin]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 16:43:13 2007''
+==See Also==
+*[[Potassium channel toxin 3D structures|Potassium channel toxin 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Tityus serrulatus]]
+[[Category: Blaustein MP]]
+[[Category: Ellis KC]]
+[[Category: Gilly WF]]
+[[Category: Tenenholz TC]]
+[[Category: Weber DJ]]

1hp2

From Proteopedia

Current revision

SOLUTION STRUCTURE OF A TOXIN FROM THE SCORPION TITYUS SERRULATUS (TSTX-K ALPHA) DETERMINED BY NMR.

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox