1t7b

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{{Seed}}
 
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[[Image:1t7b.png|left|200px]]
 
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==Crystal structure of mutant Lys8Gln of scorpion alpha-like neurotoxin BmK M1 from Buthus martensii Karsch==
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The line below this paragraph, containing "STRUCTURE_1t7b", creates the "Structure Box" on the page.
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<StructureSection load='1t7b' size='340' side='right'caption='[[1t7b]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1t7b]] 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=1T7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T7B FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t7b OCA], [https://pdbe.org/1t7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t7b RCSB], [https://www.ebi.ac.uk/pdbsum/1t7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t7b ProSAT]</span></td></tr>
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{{STRUCTURE_1t7b| PDB=1t7b | SCENE= }}
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</table>
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== Function ==
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[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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t7/1t7b_consurf.spt"</scriptWhenChecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1t7b ConSurf].
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== Publication Abstract from PubMed ==
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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.
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===Crystal structure of mutant Lys8Gln of scorpion alpha-like neurotoxin BmK M1 from Buthus martensii Karsch===
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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<ref>PMID:15321715</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1t7b" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 15321715 is the PubMed ID number.
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== References ==
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{{ABSTRACT_PUBMED_15321715}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Large Structures]]
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1T7B is a [[Single protein]] structure of 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=1T7B OCA].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15321715 15321715]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/10493862 10493862]
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Expression and purification of the BmK M1 neurotoxin from the scorpion Buthus martensii Karsch., Shao F, Xiong YM, Zhu RH, Ling MH, Chi CW, Wang DC, Protein Expr Purif. 1999 Dec;17(3):358-65. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10600453 10600453]
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The CDNA and genomic DNA sequences of a mammalian neurotoxin from the scorpion Buthus martensii Karsch., Xiong YM, Ling MH, Wang DC, Chi CW, Toxicon. 1997 Jul;35(7):1025-31. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9248001 9248001]
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[[Category: Mesobuthus martensii]]
[[Category: Mesobuthus martensii]]
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[[Category: Single protein]]
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[[Category: Guan RJ]]
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[[Category: Guan, R J.]]
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[[Category: He XL]]
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[[Category: He, X L.]]
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[[Category: Sundberg EJ]]
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[[Category: Sundberg, E J.]]
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[[Category: Wang CG]]
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[[Category: Wang, C G.]]
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[[Category: Wang DC]]
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[[Category: Wang, D C.]]
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[[Category: Wang M]]
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[[Category: Wang, M.]]
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[[Category: Xiang Y]]
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[[Category: Xiang, Y.]]
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[[Category: Zhang Y]]
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[[Category: Zhang, Y.]]
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[[Category: Bmk m1 mutant]]
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[[Category: Buthus martensii karsch]]
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[[Category: Scorpion toxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 03:56:30 2008''
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Current revision

Crystal structure of mutant Lys8Gln of scorpion alpha-like neurotoxin BmK M1 from Buthus martensii Karsch

PDB ID 1t7b

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