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1apf
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==ANTHOPLEURIN-B, NMR, 20 STRUCTURES== | ==ANTHOPLEURIN-B, NMR, 20 STRUCTURES== | ||
| - | <StructureSection load='1apf' size='340' side='right' caption='[[1apf | + | <StructureSection load='1apf' size='340' side='right'caption='[[1apf]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[1apf]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[1apf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Anthopleura_xanthogrammica Anthopleura xanthogrammica]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1APF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1APF FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <table> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1apf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1apf OCA], [https://pdbe.org/1apf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1apf RCSB], [https://www.ebi.ac.uk/pdbsum/1apf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1apf ProSAT]</span></td></tr> |
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/NA1B_ANTXA NA1B_ANTXA] Binds specifically to voltage-gated sodium channels (Nav) (site 3), thereby delaying their inactivation. This toxin has the highest affinity of all anemone toxins for the mammalian sodium channel, whereas its paralog Anthopleurin-A retains the greatest capacity to discriminate between cardiac (Nav1.5/SCN5A) and neuronal sodium channels (PubMed:8916901). When tested electrophysiologically, this toxin exhibits a high affinity for multiple sodium channels with a 50-fold preference for rat cardiac (Nav1.5/SCN5A) over neuronal channels (0.1 nM versus 5 nM). When tested by ion flux, the affinities are similar and appear to have higher affinity (9 nM versus 22 nM) (PubMed:8276803, PubMed:7612595). The residue Lys-37 of this toxin has been shown to interact with channel Nav1.5 (residue Asp-1612 in rat and Asp-1610 in human), which is located in the DIV S3-S4 linker (corresponding to channel site 3) (PubMed:9417050, PubMed:24898004). Selectively modifies sodium channel inactivation from the open state with little effect on channel activation or on inactivation from closed states (By similarity). Does not display phospholipid-binding activities, suggesting that the domain IV S3-S4 linker is located at the extracellular surface and not buried in the phospholipid bilayer (PubMed:15632158).[UniProtKB:P01530]<ref>PMID:15632158</ref> <ref>PMID:24898004</ref> <ref>PMID:7612595</ref> <ref>PMID:8276803</ref> <ref>PMID:8916901</ref> <ref>PMID:9306007</ref> <ref>PMID:9417050</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ap/1apf_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ap/1apf_consurf.spt"</scriptWhenChecked> |
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
| - | </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/ | + | </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=1apf ConSurf]. |
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | BACKGROUND: The polypeptide anthopleurin-B (AP-B) is one of a number of related toxins produced by sea anemones. AP-B delays inactivation of the voltage-gated sodium channel of excitable tissue. In the mammalian heart, this effect is manifest as an increase in the force of contraction. As a result, there is interest in exploiting the anthopleurins as lead compounds in the design of novel cardiac stimulants. Essential to this endeavour is a high-resolution solution structure of the molecule describing the positions of functionally important side chains. RESULTS: AP-B exists in multiple conformations in solution as a result of cis-trans isomerization about the Gly40-Pro41 peptide bond. The solution structure of the major conformer of AP-B has been determined by two-dimensional 1H NMR at pH 4.5 and 25 degrees C. The core structure is a four-stranded, antiparallel beta-sheet (residues 2-4, 20-23, 34-37 and 45-48) and includes several beta-turns (6-9, 25-28, 30-33). Three loops connect the beta-strands, the longest and least well defined being the first loop, extending from residues 8-17. These features are shared by other members of this family of sea anemone toxins. The locations of a number of side chains which are important for the cardiac stimulatory activity of AP-B are well defined in the structures. CONCLUSIONS: We have described the solution structure of AP-B and compared it with that of AP-A, from which it differs by substitutions at seven amino acid positions. It shares an essentially identical fold with AP-A yet is about 10-fold more active. Comparison of the structures, particularly in the region of residues essential for activity, gives a clearer indication of the location and extent of the cardioactive pharmacophore in these polypeptides. | ||
| - | |||
| - | Solution structure of the cardiostimulant polypeptide anthopleurin-B and comparison with anthopleurin-A.,Monks SA, Pallaghy PK, Scanlon MJ, Norton RS Structure. 1995 Aug 15;3(8):791-803. PMID:7582896<ref>PMID:7582896</ref> | ||
| - | |||
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Anthopleura xanthogrammica]] | [[Category: Anthopleura xanthogrammica]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Monks SA]] |
| - | [[Category: | + | [[Category: Norton RS]] |
| - | [[Category: | + | [[Category: Pallaghy PK]] |
| - | [[Category: | + | [[Category: Scanlon MJ]] |
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Current revision
ANTHOPLEURIN-B, NMR, 20 STRUCTURES
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