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== | ==THE SOLUTION STRUCTURE OF OMEGA-AGA-IVB, A P-TYPE CALCIUM CHANNEL ANTAGONIST FROM THE VENOM OF AGELENOPSIS APERTA== | ||
<StructureSection load='1agg' size='340' side='right'caption='[[1agg]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1agg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Agelenopsis_aperta Agelenopsis aperta]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AGG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AGG FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1agg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1agg OCA], [https://pdbe.org/1agg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1agg RCSB], [https://www.ebi.ac.uk/pdbsum/1agg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1agg ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/TX23B_AGEAP TX23B_AGEAP] Antagonist of voltage-gated Cav2.1/CACNA1A (P-type) calcium channels. Paralyzes insect by blocking neuromuscular transmission.<ref>PMID:8232218</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The 48 amino acid peptides omega-Aga-IVA and omega-Aga-IVB are the first agents known to specifically block P-type calcium channels in mammalian brain, thus complementing the existing suite of pharmacological tools used for characterizing calcium channels. These peptides provide a new set of probes for studies aimed at elucidating the structural basis underlying the subtype specificity of calcium channel antagonists. We used 288 NMR-derived constraints in a protocol combining distance geometry and molecular dynamics employing the program DGII, followed by energy minimization with Discover to derive the three-dimensional structure of omega-Aga-IVB. The toxin consists of a well-defined core region, comprising seven solvent-shielded residues and a well-defined triple-stranded beta-sheet. Four loop regions have average backbone rms deviations between 0.38 and 1.31 A, two of which are well-defined type-II beta-turns. Other structural features include disordered C- and N-termini and several conserved basic amino acids that are clustered on one face of the molecule. The reported structure suggests a possible surface for interaction with the channel. This surface contains amino acids that are identical to those of another known P-type calcium channel antagonist, omega-Aga-IVA, and is rich in basic residues that may have a role in binding to the anionic sites in the extracellular regions of the calcium channel. | The 48 amino acid peptides omega-Aga-IVA and omega-Aga-IVB are the first agents known to specifically block P-type calcium channels in mammalian brain, thus complementing the existing suite of pharmacological tools used for characterizing calcium channels. These peptides provide a new set of probes for studies aimed at elucidating the structural basis underlying the subtype specificity of calcium channel antagonists. We used 288 NMR-derived constraints in a protocol combining distance geometry and molecular dynamics employing the program DGII, followed by energy minimization with Discover to derive the three-dimensional structure of omega-Aga-IVB. The toxin consists of a well-defined core region, comprising seven solvent-shielded residues and a well-defined triple-stranded beta-sheet. Four loop regions have average backbone rms deviations between 0.38 and 1.31 A, two of which are well-defined type-II beta-turns. Other structural features include disordered C- and N-termini and several conserved basic amino acids that are clustered on one face of the molecule. The reported structure suggests a possible surface for interaction with the channel. This surface contains amino acids that are identical to those of another known P-type calcium channel antagonist, omega-Aga-IVA, and is rich in basic residues that may have a role in binding to the anionic sites in the extracellular regions of the calcium channel. | ||
The solution structure of omega-Aga-IVB, a P-type calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta.,Reily MD, Thanabal V, Adams ME J Biomol NMR. 1995 Feb;5(2):122-32. PMID:7703698<ref>PMID:7703698</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1agg" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Agelenopsis aperta]] | [[Category: Agelenopsis aperta]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Adams | [[Category: Adams ME]] | ||
[[Category: Reily | [[Category: Reily MD]] | ||
[[Category: Thanabal | [[Category: Thanabal V]] | ||
Latest revision as of 08:24, 5 June 2024
THE SOLUTION STRUCTURE OF OMEGA-AGA-IVB, A P-TYPE CALCIUM CHANNEL ANTAGONIST FROM THE VENOM OF AGELENOPSIS APERTATHE SOLUTION STRUCTURE OF OMEGA-AGA-IVB, A P-TYPE CALCIUM CHANNEL ANTAGONIST FROM THE VENOM OF AGELENOPSIS APERTA
Structural highlights
FunctionTX23B_AGEAP Antagonist of voltage-gated Cav2.1/CACNA1A (P-type) calcium channels. Paralyzes insect by blocking neuromuscular transmission.[1] Publication Abstract from PubMedThe 48 amino acid peptides omega-Aga-IVA and omega-Aga-IVB are the first agents known to specifically block P-type calcium channels in mammalian brain, thus complementing the existing suite of pharmacological tools used for characterizing calcium channels. These peptides provide a new set of probes for studies aimed at elucidating the structural basis underlying the subtype specificity of calcium channel antagonists. We used 288 NMR-derived constraints in a protocol combining distance geometry and molecular dynamics employing the program DGII, followed by energy minimization with Discover to derive the three-dimensional structure of omega-Aga-IVB. The toxin consists of a well-defined core region, comprising seven solvent-shielded residues and a well-defined triple-stranded beta-sheet. Four loop regions have average backbone rms deviations between 0.38 and 1.31 A, two of which are well-defined type-II beta-turns. Other structural features include disordered C- and N-termini and several conserved basic amino acids that are clustered on one face of the molecule. The reported structure suggests a possible surface for interaction with the channel. This surface contains amino acids that are identical to those of another known P-type calcium channel antagonist, omega-Aga-IVA, and is rich in basic residues that may have a role in binding to the anionic sites in the extracellular regions of the calcium channel. The solution structure of omega-Aga-IVB, a P-type calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta.,Reily MD, Thanabal V, Adams ME J Biomol NMR. 1995 Feb;5(2):122-32. PMID:7703698[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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