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1ahl

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ANTHOPLEURIN-A,NMR, 20 STRUCTURES

Structural highlights

1ahl is a 1 chain structure with sequence from Anthopleura xanthogrammica. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 20 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NA1A_ANTXA Binds specifically to voltage-gated sodium channels (Nav) (site 3), thereby delaying their inactivation. This toxin retains the greatest capacity to discriminate between the cardiac (Nav1.5/SCN5A) and neuronal sodium channels (2.5 nM versus 120 nM, when electrophysiologically tested and 14 nM versus 400 nM, when tested by ion flux), whereas its paralog Anthopleurin-B has the highest affinity of all anemone toxins for the mammalian sodium channel (PubMed:13806, PubMed:17092528, PubMed:7612595). Its ability to differentiate between cardiac and skeletal channels appears to be associated with domain 4 of the channel (PubMed:9306007). This toxin does not slow or inhibit closed-state inactivation of cardiac sodium channels, but selectively modifies inactivation from the open-state (PubMed:8576699). It 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 (By similarity).[UniProtKB:P01531]^[1] ^[2] ^[3] ^[4] ^[5]

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

The three-dimensional structure in aqueous solution of the 49-residue polypeptide anthopleurin-A (AP-A), from the sea anemone Anthopleura xanthogrammica, has been determined from 1H NMR data. A restraint set consisting of 411 interproton distance restraints inferred from NOEs and 19 backbone and 13 side chain dihedral angle restraints from spin-spin coupling constants, as well as 15 lower bound restraints based on the absence of NOEs in the spectra, was used as input for distance geometry calculations in DIANA and simulated annealing and restrained energy minimization in X-PLOR. Stereospecific assignments for 12 beta-methylene pairs were also included. The final set of 20 structures had mean pairwise rms differences over the whole molecule of 2.04 A for the backbone heavy atoms (N, C alpha, and C) and 2.59 A for all heavy atoms. For the well-defined region encompassing residues 2-7 and 17-49, the corresponding values were 0.82 and 1.27 A, respectively. AP-A adopts a compact structure consisting of four short strands of antiparallel beta-sheet (residues 2-4, 20-23, 34-37, and 45-48) connected by three loops. The first loop commences with a type I beta-turn which includes two important Asp residues; this loop is the least well-defined region of the protein, although a beta-turn involving residues 13-16 is observed in nearly half the structures. The loop linking the second and third strands is constrained by the 29-47 disulfide bond and contains two well-defined beta-turns, while the third loop contains the Gly40-Pro41 sequence, which has been identified previously as the site of cis-trans isomerism. The carboxylate group of Asp7 is close to the epsilon-ammonium group of Lys37, suggesting that they may form a salt bridge. A pH titration monitored by 2D NMR supports this by showing that Asp7 has a low pKa. It is proposed that this region of the molecule and the nearby residues Asp9 and His39 form part of the molecular surface which interacts with the mammalian cardiac sodium channel.

Three-dimensional structure in solution of the polypeptide cardiac stimulant anthopleurin-A.,Pallaghy PK, Scanlon MJ, Monks SA, Norton RS Biochemistry. 1995 Mar 21;34(11):3782-94. PMID:7893675^[6]

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

References

↑ Tanaka M, Hainu M, Yasunobu KT, Norton TR. Amino acid sequence of the Anthopleura xanthogrammica heart stimulant, anthopleurin A. Biochemistry. 1977 Jan 25;16(2):204-8. PMID:13806 doi:10.1021/bi00621a007
↑ Hanck DA, Sheets MF. Site-3 toxins and cardiac sodium channels. Toxicon. 2007 Feb;49(2):181-93. PMID:17092528 doi:10.1016/j.toxicon.2006.09.017
↑ Groome J, Lehmann-Horn F, Holzherr B. Open of a site-3 anemone toxin. Channels (Austin). 2011 Jan-Feb;5(1):65-78. PMID:21099342 doi:10.4161/chan.5.1.14031
↑ Hanck DA, Sheets MF. Modification of inactivation in cardiac sodium channels: ionic current studies with Anthopleurin-A toxin. J Gen Physiol. 1995 Oct;106(4):601-16. PMID:8576699 doi:10.1085/jgp.106.4.601
↑ Benzinger GR, Drum CL, Chen LQ, Kallen RG, Hanck DA, Hanck D. Differences in the binding sites of two site-3 sodium channel toxins. Pflugers Arch. 1997 Nov;434(6):742-9. PMID:9306007 doi:10.1007/s004240050460
↑ Pallaghy PK, Scanlon MJ, Monks SA, Norton RS. Three-dimensional structure in solution of the polypeptide cardiac stimulant anthopleurin-A. Biochemistry. 1995 Mar 21;34(11):3782-94. PMID:7893675

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/1ahl"

@@ Line 1: / Line 1: @@
 ==ANTHOPLEURIN-A,NMR, 20 STRUCTURES==
-<StructureSection load='1ahl' size='340' side='right'caption='[[1ahl]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='1ahl' size='340' side='right'caption='[[1ahl]]' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1ahl]] 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=1AHL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AHL FirstGlance]. <br>
-</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=1ahl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ahl OCA], [https://pdbe.org/1ahl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ahl RCSB], [https://www.ebi.ac.uk/pdbsum/1ahl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ahl ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=1ahl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ahl OCA], [https://pdbe.org/1ahl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ahl RCSB], [https://www.ebi.ac.uk/pdbsum/1ahl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ahl ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/TXAA_ANTXA TXAA_ANTXA]] Binds specifically to the sodium channel (Nav), thereby delaying its inactivation during signal transduction. Thus it strongly stimulates mammalian cardiac muscle contraction.
+[https://www.uniprot.org/uniprot/NA1A_ANTXA NA1A_ANTXA] Binds specifically to voltage-gated sodium channels (Nav) (site 3), thereby delaying their inactivation. This toxin retains the greatest capacity to discriminate between the cardiac (Nav1.5/SCN5A) and neuronal sodium channels (2.5 nM versus 120 nM, when electrophysiologically tested and 14 nM versus 400 nM, when tested by ion flux), whereas its paralog Anthopleurin-B has the highest affinity of all anemone toxins for the mammalian sodium channel (PubMed:13806, PubMed:17092528, PubMed:7612595). Its ability to differentiate between cardiac and skeletal channels appears to be associated with domain 4 of the channel (PubMed:9306007). This toxin does not slow or inhibit closed-state inactivation of cardiac sodium channels, but selectively modifies inactivation from the open-state (PubMed:8576699). It 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 (By similarity).[UniProtKB:P01531]<ref>PMID:13806</ref> <ref>PMID:17092528</ref> <ref>PMID:21099342</ref> <ref>PMID:8576699</ref> <ref>PMID:9306007</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 13: / Line 14: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ah/1ahl_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 33: / Line 34: @@
 [[Category: Anthopleura xanthogrammica]]
 [[Category: Large Structures]]
-[[Category: Monks, S A]]
+[[Category: Monks SA]]
-[[Category: Norton, R S]]
+[[Category: Norton RS]]
-[[Category: Pallaghy, P K]]
+[[Category: Pallaghy PK]]
-[[Category: Scanlon, M J]]
+[[Category: Scanlon MJ]]
-[[Category: Cardiac stimulant]]
-[[Category: Neurotoxin]]

1ahl

From Proteopedia

Current revision

ANTHOPLEURIN-A,NMR, 20 STRUCTURES

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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