This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2kni

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:46, 14 June 2023) (edit) (undo)
 
(9 intermediate revisions not shown.)
Line 1: Line 1:
-
{{Seed}}
 
-
[[Image:2kni.jpg|left|200px]]
 
-
<!--
+
==High-resolution solution structure of the ASIC1a blocker PcTX1==
-
The line below this paragraph, containing "STRUCTURE_2kni", creates the "Structure Box" on the page.
+
<StructureSection load='2kni' size='340' side='right'caption='[[2kni]]' 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'>[[2kni]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Psalmopoeus_cambridgei Psalmopoeus cambridgei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KNI 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=2kni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kni OCA], [https://pdbe.org/2kni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kni RCSB], [https://www.ebi.ac.uk/pdbsum/2kni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kni ProSAT]</span></td></tr>
-
-->
+
</table>
-
{{STRUCTURE_2kni| PDB=2kni | SCENE= }}
+
== Function ==
 +
[https://www.uniprot.org/uniprot/TXP1_PSACA TXP1_PSACA] Potently and selectively blocks the acid-sensing ion channel ASIC1a/ACCN2. The blockade is rapid and reversible. Psalmotoxin 1 loses its capacity to block ASIC1a/ACCN2 as soon as this subunit is associated with another member of the family (ASIC2a/ACCN1 or ASIC3/ACCN3). The toxin can distinguish between the two ASIC1/ACCN2 splice variants ASIC1a/ACCN2 and ASIC1b/ACCN2.<ref>PMID:10829030</ref>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Acid-sensing ion channel 1a (ASIC1a) is a primary acid sensor in the peripheral and central nervous system. It has been implicated as a novel therapeutic target for a broad range of pathophysiological conditions including pain, ischemic stroke, depression, and autoimmune diseases such as multiple sclerosis. The only known selective blocker of ASIC1a is pi-TRTX-Pc1a (PcTx1), a disulfide-rich 40-residue peptide isolated from spider venom. pi-TRTX-Pc1a is an effective analgesic in rodent models of acute pain and it provides neuroprotection in a mouse model of ischemic stroke. Thus, understanding the molecular basis of the pi-TRTX-Pc1a-ASIC1a interaction should facilitate development of therapeutically useful ASIC1a blockers. We therefore developed an efficient bacterial expression system to produce a panel of pi-TRTX-Pc1a mutants for probing structure-activity relationships as well as isotopically labeled toxin for determination of its solution structure and dynamics. We demonstrate that the toxin pharmacophore resides in a beta-hairpin loop that was revealed to be mobile over a wide range of time scales using molecular dynamics simulations in combination with NMR spin relaxation and relaxation dispersion measurements. The toxin-receptor interaction was modeled by in silico docking of the toxin structure onto a homology model of rat ASIC1a in a restraints-driven approach that was designed to take account of the dynamics of the toxin pharmacophore and the consequent remodeling of side-chain conformations upon receptor binding. The resulting model reveals new insights into the mechanism of action of pi-TRTX-Pc1a and provides an experimentally validated template for the rational design of therapeutically useful pi-TRTX-Pc1a mimetics.
-
===High-resolution solution structure of the ASIC1a blocker PcTX1===
+
A dynamic pharmacophore drives the interaction between Psalmotoxin-1 and the putative drug target acid-sensing ion channel 1a.,Saez NJ, Mobli M, Bieri M, Chassagnon IR, Malde AK, Gamsjaeger R, Mark AE, Gooley PR, Rash LD, King GF Mol Pharmacol. 2011 Nov;80(5):796-808. doi: 10.1124/mol.111.072207. Epub 2011 Aug, 8. PMID:21825095<ref>PMID:21825095</ref>
-
 
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
==About this Structure==
+
</div>
-
2KNI is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Psalmopoeus_cambridgei Psalmopoeus cambridgei]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KNI OCA].
+
<div class="pdbe-citations 2kni" style="background-color:#fffaf0;"></div>
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:12824480</ref><references group="xtra"/>
+
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Psalmopoeus cambridgei]]
[[Category: Psalmopoeus cambridgei]]
-
[[Category: King, G F.]]
+
[[Category: King GF]]
-
[[Category: Mobli, M.]]
+
[[Category: Mobli M]]
-
[[Category: Saez, N J.]]
+
[[Category: Saez NJ]]
-
[[Category: Acid sensing ion channel 1a inhibitor]]
+
-
[[Category: Asic1a inhibitor]]
+
-
[[Category: Cystine knot]]
+
-
[[Category: Disulfide bond]]
+
-
[[Category: Ionic channel inhibitor]]
+
-
[[Category: Knottin]]
+
-
[[Category: Neurotoxin]]
+
-
[[Category: Peptide toxin]]
+
-
[[Category: Pi-theraphotoxin-pc1a]]
+
-
[[Category: Psalmotoxin 1]]
+
-
[[Category: Secreted]]
+
-
[[Category: Spider toxin]]
+
-
[[Category: Toxin]]
+
-
 
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Sep 1 09:43:27 2010''
+

Current revision

High-resolution solution structure of the ASIC1a blocker PcTX1

PDB ID 2kni

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kni"
Personal tools