1agg
From Proteopedia
(New page: 200px<br /><applet load="1agg" size="450" color="white" frame="true" align="right" spinBox="true" caption="1agg" /> '''THE SOLUTION STRUCTURE OF OMEGA-AGA-IVB, A P...) |
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'''THE SOLUTION STRUCTURE OF OMEGA-AGA-IVB, A P-TYPE CALCIUM CHANNEL ANTAGONIST FROM THE VENOM OF AGELENOPSIS APERTA'''<br /> | '''THE SOLUTION STRUCTURE OF OMEGA-AGA-IVB, A P-TYPE CALCIUM CHANNEL ANTAGONIST FROM THE VENOM OF AGELENOPSIS APERTA'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The 48 amino acid peptides omega-Aga-IVA and omega-Aga-IVB are the first | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1AGG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Agelenopsis_aperta Agelenopsis aperta]. Full crystallographic information is available from [http:// | + | 1AGG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Agelenopsis_aperta Agelenopsis aperta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AGG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Agelenopsis aperta]] | [[Category: Agelenopsis aperta]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Adams, M | + | [[Category: Adams, M E.]] |
| - | [[Category: Reily, M | + | [[Category: Reily, M D.]] |
[[Category: Thanabal, V.]] | [[Category: Thanabal, V.]] | ||
[[Category: neurotoxin]] | [[Category: neurotoxin]] | ||
[[Category: p-type calcium channel antagonist]] | [[Category: p-type calcium channel antagonist]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:44:16 2008'' |
Revision as of 09:44, 21 February 2008
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THE SOLUTION STRUCTURE OF OMEGA-AGA-IVB, A P-TYPE CALCIUM CHANNEL ANTAGONIST FROM THE VENOM OF AGELENOPSIS APERTA
Overview
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.
About this Structure
1AGG is a Single protein structure of sequence from Agelenopsis aperta. Full crystallographic information is available from OCA.
Reference
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
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