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1t7a

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Revision as of 16:48, 25 December 2014

Crystal structure of mutant Lys8Asp of scorpion alpha-like neurotoxin BmK M1 from Buthus martensii Karsch

Structural highlights

1t7a 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.
Related:	1sn1, 1t7b, 1t7e
Gene:	BmK M1 (Mesobuthus martensii)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[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.^[1] ^[2]

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

Non-proline cis peptide bonds have been observed in numerous protein crystal structures even though the energetic barrier to this conformation is significant and no non-prolyl-cis/trans-isomerase has been identified to date. While some external factors, such as metal binding or co-factor interaction, have been identified that appear to induce cis/trans isomerization of non-proline peptide bonds, the intrinsic structural basis for their existence and the mechanism governing cis/trans isomerization in proteins remains poorly understood. Here, we report the crystal structure of a newly isolated neurotoxin, the scorpion alpha-like toxin Buthus martensii Karsch (BmK) M7, at 1.4A resolution. BmK M7 crystallizes as a dimer in which the identical non-proline peptide bond between residues 9 and 10 exists either in the cis conformation or as a mixture of cis and trans conformations in either monomer. We also determined the crystal structures of several mutants of BmK M1, a representative scorpion alpha-like toxin that contains an identical non-proline cis peptide bond as that observed in BmK M7, in which residues within or neighboring the cis peptide bond were altered. Substitution of an aspartic acid residue for lysine at residue 8 in the BmK M1 (K8D) mutant converted the cis form of the non-proline peptide bond 9-10 into the trans form, revealing an intramolecular switch for cis-to-trans isomerization. Cis/trans interconversion of the switch residue at position 8 appears to be sequence-dependent as the peptide bond between residues 9 and 10 retains its wild-type cis conformation in the BmK M1 (K8Q) mutant structure. The structural interconversion of the isomeric states of the BmK M1 non-proline cis peptide bond may relate to the conversion of the scorpion alpha-toxins subgroups.

Structural mechanism governing cis and trans isomeric states and an intramolecular switch for cis/trans isomerization of a non-proline peptide bond observed in crystal structures of scorpion toxins.,Guan RJ, Xiang Y, He XL, Wang CG, Wang M, Zhang Y, Sundberg EJ, Wang DC J Mol Biol. 2004 Aug 27;341(5):1189-204. PMID:15321715^[3]

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
↑ Guan RJ, Xiang Y, He XL, Wang CG, Wang M, Zhang Y, Sundberg EJ, Wang DC. Structural mechanism governing cis and trans isomeric states and an intramolecular switch for cis/trans isomerization of a non-proline peptide bond observed in crystal structures of scorpion toxins. J Mol Biol. 2004 Aug 27;341(5):1189-204. PMID:15321715 doi:http://dx.doi.org/10.1016/j.jmb.2004.06.067

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1t7a"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1t7a]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mesobuthus_martensii Mesobuthus martensii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T7A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T7A FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sn1|1sn1]], [[1t7b|1t7b]], [[1t7e|1t7e]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1sn1|1sn1]], [[1t7b|1t7b]], [[1t7e|1t7e]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BmK M1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=34649 Mesobuthus martensii])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BmK M1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=34649 Mesobuthus martensii])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t7a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t7a RCSB], [http://www.ebi.ac.uk/pdbsum/1t7a PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t7a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t7a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1t7a RCSB], [http://www.ebi.ac.uk/pdbsum/1t7a PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 30: / Line 32: @@
 </StructureSection>
 [[Category: Mesobuthus martensii]]
-[[Category: Guan, R J.]]
+[[Category: Guan, R J]]
-[[Category: He, X L.]]
+[[Category: He, X L]]
-[[Category: Sundberg, E J.]]
+[[Category: Sundberg, E J]]
-[[Category: Wang, C G.]]
+[[Category: Wang, C G]]
-[[Category: Wang, D C.]]
+[[Category: Wang, D C]]
-[[Category: Wang, M.]]
+[[Category: Wang, M]]
-[[Category: Xiang, Y.]]
+[[Category: Xiang, Y]]
-[[Category: Zhang, Y.]]
+[[Category: Zhang, Y]]
 [[Category: Cis/trans isomerization]]
 [[Category: Intramolecular switch]]

1t7a

From Proteopedia

Revision as of 16:48, 25 December 2014

Crystal structure of mutant Lys8Asp of scorpion alpha-like neurotoxin BmK M1 from Buthus martensii Karsch

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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