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| - | [[Image:2h7z.gif|left|200px]] | |
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| - | <!-- | + | ==Crystal structure of irditoxin== |
| - | The line below this paragraph, containing "STRUCTURE_2h7z", creates the "Structure Box" on the page.
| + | <StructureSection load='2h7z' size='340' side='right'caption='[[2h7z]], [[Resolution|resolution]] 1.50Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet) | + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[2h7z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Boiga_irregularis Boiga irregularis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H7Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2H7Z FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </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=2h7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2h7z OCA], [https://pdbe.org/2h7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2h7z RCSB], [https://www.ebi.ac.uk/pdbsum/2h7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2h7z ProSAT]</span></td></tr> |
| - | --> | + | </table> |
| - | {{STRUCTURE_2h7z| PDB=2h7z | SCENE= }}
| + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h7/2h7z_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </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/main_output.php?pdb_ID=2h7z ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | A novel heterodimeric three-finger neurotoxin, irditoxin, was isolated from venom of the brown treesnake Boiga irregularis (Colubridae). Irditoxin subunit amino acid sequences were determined by Edman degradation and cDNA sequencing. The crystal structure revealed two subunits with a three-finger protein fold, typical for "nonconventional" toxins such as denmotoxin, bucandin, and candoxin. This is the first colubrid three-finger toxin dimer, covalently connected via an interchain disulfide bond. Irditoxin showed taxon-specific lethality toward birds and lizards and was nontoxic toward mice. It produced a potent neuromuscular blockade at the avian neuromuscular junction (IC(50)=10 nM), comparable to alpha-bungarotoxin, but was three orders of magnitude less effective at the mammalian neuromuscular junction. Covalently linked heterodimeric three-finger toxins found in colubrid venoms constitute a new class of venom peptides, which may be a useful source of new neurobiology probes and therapeutic leads. |
| | | | |
| - | '''Crystal structure of irditoxin'''
| + | Irditoxin, a novel covalently linked heterodimeric three-finger toxin with high taxon-specific neurotoxicity.,Pawlak J, Mackessy SP, Sixberry NM, Stura EA, Le Du MH, Menez R, Foo CS, Menez A, Nirthanan S, Kini RM FASEB J. 2009 Feb;23(2):534-45. Epub 2008 Oct 24. PMID:18952712<ref>PMID:18952712</ref> |
| | | | |
| - | | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | ==Overview==
| + | </div> |
| - | Boiga dendrophila (mangrove catsnake) is a colubrid snake that lives in Southeast Asian lowland rainforests and mangrove swamps and that preys primarily on birds. We have isolated, purified, and sequenced a novel toxin from its venom, which we named denmotoxin. It is a monomeric polypeptide of 77 amino acid residues with five disulfide bridges. In organ bath experiments, it displayed potent postsynaptic neuromuscular activity and irreversibly inhibited indirectly stimulated twitches in chick biventer cervicis nerve-muscle preparations. In contrast, it induced much smaller and readily reversible inhibition of electrically induced twitches in mouse hemidiaphragm nerve-muscle preparations. More precisely, the chick muscle alpha(1)betagammadelta-nicotinic acetylcholine receptor was 100-fold more susceptible compared with the mouse receptor. These data indicate that denmotoxin has a bird-specific postsynaptic activity. We chemically synthesized denmotoxin, crystallized it, and solved its crystal structure at 1.9 A by the molecular replacement method. The toxin structure adopts a non-conventional three-finger fold with an additional (fifth) disulfide bond in the first loop and seven additional residues at its N terminus, which is blocked by a pyroglutamic acid residue. This is the first crystal structure of a three-finger toxin from colubrid snake venom and the first fully characterized bird-specific toxin. Denmotoxin illustrates the relationship between toxin specificity and the primary prey type that constitutes the snake's diet.
| + | <div class="pdbe-citations 2h7z" style="background-color:#fffaf0;"></div> |
| - | | + | == References == |
| - | ==About this Structure== | + | <references/> |
| - | 2H7Z is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Boiga_irregularis Boiga irregularis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2H7Z OCA].
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==Reference== | + | |
| - | Denmotoxin, a three-finger toxin from the colubrid snake Boiga dendrophila (Mangrove Catsnake) with bird-specific activity., Pawlak J, Mackessy SP, Fry BG, Bhatia M, Mourier G, Fruchart-Gaillard C, Servent D, Menez R, Stura E, Menez A, Kini RM, J Biol Chem. 2006 Sep 29;281(39):29030-41. Epub 2006 Jul 24. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16864572 16864572]
| + | |
| | [[Category: Boiga irregularis]] | | [[Category: Boiga irregularis]] |
| - | [[Category: Protein complex]] | + | [[Category: Large Structures]] |
| - | [[Category: Du, M H.Le.]] | + | [[Category: Du, M H.Le]] |
| - | [[Category: Kini, R M.]] | + | [[Category: Kini, R M]] |
| - | [[Category: Pawlak, J.]] | + | [[Category: Pawlak, J]] |
| - | [[Category: Stura, E A.]] | + | [[Category: Stura, E A]] |
| | [[Category: Neurotoxin]] | | [[Category: Neurotoxin]] |
| | [[Category: Snake venom]] | | [[Category: Snake venom]] |
| | [[Category: Three-finger toxin]] | | [[Category: Three-finger toxin]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:58:39 2008''
| + | [[Category: Toxin]] |
| Structural highlights
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
A novel heterodimeric three-finger neurotoxin, irditoxin, was isolated from venom of the brown treesnake Boiga irregularis (Colubridae). Irditoxin subunit amino acid sequences were determined by Edman degradation and cDNA sequencing. The crystal structure revealed two subunits with a three-finger protein fold, typical for "nonconventional" toxins such as denmotoxin, bucandin, and candoxin. This is the first colubrid three-finger toxin dimer, covalently connected via an interchain disulfide bond. Irditoxin showed taxon-specific lethality toward birds and lizards and was nontoxic toward mice. It produced a potent neuromuscular blockade at the avian neuromuscular junction (IC(50)=10 nM), comparable to alpha-bungarotoxin, but was three orders of magnitude less effective at the mammalian neuromuscular junction. Covalently linked heterodimeric three-finger toxins found in colubrid venoms constitute a new class of venom peptides, which may be a useful source of new neurobiology probes and therapeutic leads.
Irditoxin, a novel covalently linked heterodimeric three-finger toxin with high taxon-specific neurotoxicity.,Pawlak J, Mackessy SP, Sixberry NM, Stura EA, Le Du MH, Menez R, Foo CS, Menez A, Nirthanan S, Kini RM FASEB J. 2009 Feb;23(2):534-45. Epub 2008 Oct 24. PMID:18952712[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pawlak J, Mackessy SP, Sixberry NM, Stura EA, Le Du MH, Menez R, Foo CS, Menez A, Nirthanan S, Kini RM. Irditoxin, a novel covalently linked heterodimeric three-finger toxin with high taxon-specific neurotoxicity. FASEB J. 2009 Feb;23(2):534-45. Epub 2008 Oct 24. PMID:18952712 doi:10.1096/fj.08-113555
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