View source for 2asp


==Structure of Rabbit Actin In Complex With Reidispongiolide C==
<StructureSection load='2asp' size='340' side='right'caption='[[2asp]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2asp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ASP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ASP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.64&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=RGC:REIDISPONGIOLIDE+C'>RGC</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=2asp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2asp OCA], [https://pdbe.org/2asp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2asp RCSB], [https://www.ebi.ac.uk/pdbsum/2asp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2asp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACTS_RABIT ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
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== Publication Abstract from PubMed ==
Marine macrolides that disrupt the actin cytoskeleton are promising candidates for cancer treatment. Here, we present the actin-bound x-ray crystal structures of reidispongiolide A and C and sphinxolide B, three marine macrolides found among a recently discovered family of cytotoxic compounds. Their structures allow unequivocal assignment of the absolute configuration for each compound. A comparison of their actin-binding site to macrolides found in the trisoxazole family, as well as the divalent macrolide, swinholide A, reveals the existence of a common binding surface for a defined segment of their macrocyclic ring. This surface is located on a hydrophobic patch adjacent to the cleft separating domains 1 and 3 at the barbed-end of actin. The large area surrounding this surface accommodates a wide variety of conformations and designs observed in the macrocyclic component of barbed-end-targeting macrolides. Conversely, the binding pocket for the macrolide tail, located within the cleft itself, shows very limited variation. Functional characterization of these macrolides by using in vitro actin filament severing and polymerization assays demonstrate the necessity of the N-methyl-vinylformamide moiety at the terminus of the macrolide tail for toxin potency. These analyses also show the importance of stable interactions between the macrocyclic ring and the hydrophobic patch on actin for modifying filament structure and how this stability can be compromised by subtle changes in macrolactone ring composition. By identifying the essential components of these complex natural products that underlie their high actin affinity, we have established a framework for designing new therapeutic agents.

Structures of microfilament destabilizing toxins bound to actin provide insight into toxin design and activity.,Allingham JS, Zampella A, D'Auria MV, Rayment I Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14527-32. Epub 2005 Sep 28. PMID:16192358<ref>PMID:16192358</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2asp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Actin 3D structures|Actin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Oryctolagus cuniculus]]
[[Category: Allingham JS]]
[[Category: D'Auria MV]]
[[Category: Rayment I]]
[[Category: Zampella A]]