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1sn1

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Revision as of 23:49, 27 December 2023

STRUCTURE OF SCORPION NEUROTOXIN BMK M1

Structural highlights

1sn1 is a 1 chain structure with sequence from Mesobuthus martensii. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SCM1_MESMA Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels thereby blocking neuronal transmission. This toxin is active against both mammals and insects, and is classified as an alpha-like toxin. It is active on Nav1.2/SCN2A (EC(50)=139-252 nM), Nav1.3/SCN3A (EC(50)=565 nM), Nav1.4/SCN4A and Nav1.5/SCN5A (EC(50)=195-500 nM), Nav1.6/SCN8A (EC(50)=214 nM), and drosophila DmNav1 (EC(50)=30 nM) (PubMed:11322948, PubMed:12705833, PubMed:15677695, PubMed:19162162, PubMed:20678086). In mNav1.6/SCN8A, the toxin induces a large increase in both transient and persistent currents, which correlates with a prominent reduction in the fast component of inactivating current (PubMed:20678086). In rNav1.2/SCN2A and rNav1.3/SCN3A, toxin-increased currents is much smaller (PubMed:19162162, PubMed:20678086). Moreover, the toxin only accelerates the slow inactivation development and delay recovery of mNav1.6/SCN8A through binding to the channel in the open state (PubMed:20678086). Is 6-fold more toxic than BmK-M2. In vivo, intrahippocampal injection into rat induces epileptiform responses (PubMed:16229835). In addition, intraplantar injection into rat induces spontaneous nociception and hyperalgesia (PubMed:14554105).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The crystal structures of two group III alpha-like toxins from the scorpion Buthus martensii Karsch, BmK M1 and BmK M4, were determined at 1.7 A and 1.3 A resolution and refined to R factors of 0.169 and 0.166, respectively. The first high-resolution structures of the alpha-like scorpion toxin show some striking features compared with structures of the "classical" alpha-toxin. Firstly, a non-proline cis peptide bond between residues 9 and 10 unusually occurs in the five-member reverse turn 8-12. Secondly, the cis peptide 9-10 mediates the spatial relationship between the turn 8-12 and the C-terminal stretch 58-64 through a pair of main-chain hydrogen bonds between residues 10 and 64 to form a unique tertiary arrangement which features the special orientation of the terminal residues 62-64. Finally, in consequence of the peculiar orientation of the C-terminal residues, the functional groups of Arg58, which are crucial for the toxin-receptor interaction, are exposed and accessible in BmK M1 and M4 rather than buried as in the classical alpha-toxins. Sequence alignment and characteristics analysis suggested that the above structural features observed in BmK M1 and M4 occur in all group III alpha-like toxins. Recently, some group III alpha-like toxins were demonstrated to occupy a receptor site different from the classical alpha-toxin. Therefore, the distinct structural features of BmK M1 and M4 presented here may provide the structural basis for the newly recognized toxin-receptor binding site selectivity. Besides, the non-proline cis peptide bonds found in these two structures play a role in the formation of the structural characteristics and in keeping accurate positions of the functionally crucial residues. This manifested a way to achieve high levels of molecular specificity and atomic precision through the strained backbone geometry.

Crystal structures of two alpha-like scorpion toxins: non-proline cis peptide bonds and implications for new binding site selectivity on the sodium channel.,He XL, Li HM, Zeng ZH, Liu XQ, Wang M, Wang DC J Mol Biol. 1999 Sep 10;292(1):125-35. PMID:10493862^[8]

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

References

↑ Goudet C, Huys I, Clynen E, Schoofs L, Wang DC, Waelkens E, Tytgat J. Electrophysiological characterization of BmK M1, an alpha-like toxin from Buthus martensi Karsch venom. FEBS Lett. 2001 Apr 20;495(1-2):61-5. PMID:11322948
↑ Wang CG, Gilles N, Hamon A, Le Gall F, Stankiewicz M, Pelhate M, Xiong YM, Wang DC, Chi CW. Exploration of the functional site of a scorpion alpha-like toxin by site-directed mutagenesis. Biochemistry. 2003 Apr 29;42(16):4699-708. PMID:12705833 doi:http://dx.doi.org/10.1021/bi0270438
↑ Bai ZT, Zhang XY, Ji YH. Fos expression in rat spinal cord induced by peripheral injection of BmK I, an alpha-like scorpion neurotoxin. Toxicol Appl Pharmacol. 2003 Oct 1;192(1):78-85. PMID:14554105 doi:10.1016/s0041-008x(03)00260-6
↑ Liu LH, Bosmans F, Maertens C, Zhu RH, Wang DC, Tytgat J. Molecular basis of the mammalian potency of the scorpion alpha-like toxin, BmK M1. FASEB J. 2005 Apr;19(6):594-6. PMID:15677695 doi:10.1096/fj.04-2485fje
↑ Bai ZT, Zhao R, Zhang XY, Chen J, Liu T, Ji YH. The epileptic seizures induced by BmK I, a modulator of sodium channels. Exp Neurol. 2006 Jan;197(1):167-76. PMID:16229835 doi:10.1016/j.expneurol.2005.09.006
↑ Zhu MM, Tan M, Cheng HW, Ji YH. The alpha-like scorpion toxin BmK I enhances membrane excitability via persistent sodium current by preventing slow inactivation and deactivation of rNav1.2a expressed in Xenopus Oocytes. Toxicol In Vitro. 2009 Jun;23(4):561-8. PMID:19162162 doi:10.1016/j.tiv.2008.12.022
↑ He H, Liu Z, Dong B, Zhou J, Zhu H, Ji Y. Molecular determination of selectivity of the site 3 modulator (BmK I) to sodium channels in the CNS: a clue to the importance of Nav1.6 in BmK I-induced neuronal hyperexcitability. Biochem J. 2010 Oct 15;431(2):289-98. PMID:20678086 doi:10.1042/BJ20100517
↑ He XL, Li HM, Zeng ZH, Liu XQ, Wang M, Wang DC. Crystal structures of two alpha-like scorpion toxins: non-proline cis peptide bonds and implications for new binding site selectivity on the sodium channel. J Mol Biol. 1999 Sep 10;292(1):125-35. PMID:10493862 doi:http://dx.doi.org/10.1006/jmbi.1999.3036

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1sn1"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1sn1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mesobuthus_martensii Mesobuthus martensii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SN1 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1sn4|1sn4]]</div></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</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=1sn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sn1 OCA], [https://pdbe.org/1sn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1sn1 RCSB], [https://www.ebi.ac.uk/pdbsum/1sn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1sn1 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/SCX1_MESMA SCX1_MESMA]] This alpha-like toxin binds voltage-dependently sodium channels and inhibits the inactivation of the activated channels, thereby blocking neuronal transmission. This toxin is active against mammals and insects. Is active on Nav1.4/SCN4A and Nav1.5/SCN5A. Acts as a cardiotoxin. Is 6-fold more toxic than BmK-M2.<ref>PMID:11322948</ref> <ref>PMID:12705833</ref>
+[https://www.uniprot.org/uniprot/SCM1_MESMA SCM1_MESMA] Alpha toxins bind voltage-independently at site-3 of sodium channels (Nav) and inhibit the inactivation of the activated channels thereby blocking neuronal transmission. This toxin is active against both mammals and insects, and is classified as an alpha-like toxin. It is active on Nav1.2/SCN2A (EC(50)=139-252 nM), Nav1.3/SCN3A (EC(50)=565 nM), Nav1.4/SCN4A and Nav1.5/SCN5A (EC(50)=195-500 nM), Nav1.6/SCN8A (EC(50)=214 nM), and drosophila DmNav1 (EC(50)=30 nM) (PubMed:11322948, PubMed:12705833, PubMed:15677695, PubMed:19162162, PubMed:20678086). In mNav1.6/SCN8A, the toxin induces a large increase in both transient and persistent currents, which correlates with a prominent reduction in the fast component of inactivating current (PubMed:20678086). In rNav1.2/SCN2A and rNav1.3/SCN3A, toxin-increased currents is much smaller (PubMed:19162162, PubMed:20678086). Moreover, the toxin only accelerates the slow inactivation development and delay recovery of mNav1.6/SCN8A through binding to the channel in the open state (PubMed:20678086). Is 6-fold more toxic than BmK-M2. In vivo, intrahippocampal injection into rat induces epileptiform responses (PubMed:16229835). In addition, intraplantar injection into rat induces spontaneous nociception and hyperalgesia (PubMed:14554105).<ref>PMID:11322948</ref> <ref>PMID:12705833</ref> <ref>PMID:14554105</ref> <ref>PMID:15677695</ref> <ref>PMID:16229835</ref> <ref>PMID:19162162</ref> <ref>PMID:20678086</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 37: @@
 [[Category: Large Structures]]
 [[Category: Mesobuthus martensii]]
-[[Category: He, X L]]
+[[Category: He XL]]
-[[Category: Li, H M]]
+[[Category: Li HM]]
-[[Category: Liu, X Q]]
+[[Category: Liu XQ]]
-[[Category: Wang, D C]]
+[[Category: Wang DC]]
-[[Category: Zeng, Z H]]
+[[Category: Zeng ZH]]
-[[Category: Neurotoxin]]
-[[Category: Scorpion]]
-[[Category: Sodium channel inhibitor]]
-[[Category: Toxin]]

1sn1

From Proteopedia

Revision as of 23:49, 27 December 2023

STRUCTURE OF SCORPION NEUROTOXIN BMK M1

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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