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4lft

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Structure of alpha-elapitoxin-Dpp2d isolated from Black Mamba (Dendroaspis polylepis) venom

Structural highlights

4lft is a 2 chain structure with sequence from Dendroaspis polylepis polylepis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.7Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

3L21_DENPO

Publication Abstract from PubMed

We isolated a novel, atypical long-chain three-finger toxin (TFT), alpha-elapitoxin-Dpp2d (alpha-EPTX-Dpp2d), from black mamba (Dendroaspis polylepis polylepis) venom. Proteolytic digestion with trypsin and V8 protease, together with MS/MS de novo sequencing, indicated that the mature toxin has an amidated C-terminal arginine, a posttranslational modification rarely observed for snake TFTs. alpha-EPTX-Dpp2d was found to potently inhibit alpha7 neuronal nicotinic acetylcholine receptors (nAChR; IC50, 58 +/- 24 nM) and muscle-type nAChR (IC50, 114 +/- 37 nM) but did not affect alpha3beta2 and alpha3beta4 nAChR isoforms at 1 muM concentrations. Competitive radioligand binding assays demonstrated that alpha-EPTX-Dpp2d competes with epibatidine binding to the Lymnea stagnalis acetylcholine-binding protein (Ls-AChBP; IC50, 4.9 +/- 2.3 nM). The activity profile and binding data are reminiscent of classical long-chain TFTs with a free carboxyl termini, suggesting that amidation does not significantly affect toxin selectivity. The crystal structure of alpha-EPTX-Dpp2d was determined at 1.7 A resolution and displayed a dimeric toxin assembly with each monomer positioned in an antiparallel orientation. The dimeric structure is stabilized by extensive intermolecular hydrogen bonds and electrostatic interactions, which raised the possibility that the toxin may exist as a noncovalent homodimer in solution. However, chemical cross-linking and size-exclusion chromatography coupled with multiangle laser light scattering (MALLS) data indicated that the toxin is predominantly monomeric under physiological conditions. Because of its high potency and selectivity, we expect this toxin to be a valuable pharmacological tool for studying the structure and function of nAChRs.

Isolation and Structural and Pharmacological Characterization of alpha-Elapitoxin-Dpp2d, an Amidated Three Finger Toxin from Black Mamba Venom.,Wang CI, Reeks T, Vetter I, Vergara I, Kovtun O, Lewis RJ, Alewood PF, Durek T Biochemistry. 2014 Jun 5. PMID:24867092^[1]

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

References

↑ Wang CI, Reeks T, Vetter I, Vergara I, Kovtun O, Lewis RJ, Alewood PF, Durek T. Isolation and Structural and Pharmacological Characterization of alpha-Elapitoxin-Dpp2d, an Amidated Three Finger Toxin from Black Mamba Venom. Biochemistry. 2014 Jun 5. PMID:24867092 doi:http://dx.doi.org/10.1021/bi5004475

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4lft"

@@ Line 1: / Line 1: @@
 ==Structure of alpha-elapitoxin-Dpp2d isolated from Black Mamba (Dendroaspis polylepis) venom==
-<StructureSection load='4lft' size='340' side='right' caption='[[4lft]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+<StructureSection load='4lft' size='340' side='right'caption='[[4lft]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4lft]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Dendroaspis_polylepis_polylepis Dendroaspis polylepis polylepis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LFT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LFT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4lft]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Dendroaspis_polylepis_polylepis Dendroaspis polylepis polylepis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LFT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LFT FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4lft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lft OCA], [http://pdbe.org/4lft PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lft RCSB], [http://www.ebi.ac.uk/pdbsum/4lft PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lft ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=4lft FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lft OCA], [https://pdbe.org/4lft PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lft RCSB], [https://www.ebi.ac.uk/pdbsum/4lft PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lft ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/3L21_DENPO 3L21_DENPO]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 24: @@
 </StructureSection>
 [[Category: Dendroaspis polylepis polylepis]]
-[[Category: Alewood, P F]]
+[[Category: Large Structures]]
-[[Category: Durek, T]]
+[[Category: Alewood PF]]
-[[Category: Lewis, R J]]
+[[Category: Durek T]]
-[[Category: Reeks, T]]
+[[Category: Lewis RJ]]
-[[Category: Wang, C I.A]]
+[[Category: Reeks T]]
-[[Category: Acetylcholine receptor inhibitor activity]]
+[[Category: Wang CIA]]
-[[Category: Disulfide-rich]]
-[[Category: Expressed by the venom gland]]
-[[Category: Long neurotoxin]]
-[[Category: Three-finger-toxin]]
-[[Category: Toxin]]

4lft

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Current revision

Structure of alpha-elapitoxin-Dpp2d isolated from Black Mamba (Dendroaspis polylepis) venom

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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