|
|
| Line 4: |
Line 4: |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2aso]] 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=2ASO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ASO FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2aso]] 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=2ASO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ASO FirstGlance]. <br> |
| - | </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=SPX:SPHINXOLIDE+B'>SPX</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HIC:4-METHYL-HISTIDINE'>HIC</scene></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=HIC:4-METHYL-HISTIDINE'>HIC</scene>, <scene name='pdbligand=SPX:SPHINXOLIDE+B'>SPX</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1qz5|1qz5]], [[1qz6|1qz6]], [[1s22|1s22]], [[2asm|2asm]], [[2asp|2asp]]</div></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=2aso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aso OCA], [https://pdbe.org/2aso PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aso RCSB], [https://www.ebi.ac.uk/pdbsum/2aso PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aso ProSAT]</span></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=2aso FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2aso OCA], [https://pdbe.org/2aso PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2aso RCSB], [https://www.ebi.ac.uk/pdbsum/2aso PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2aso ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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.
| + | [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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 29: |
Line 28: |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Oryctolagus cuniculus]] | | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Allingham, J S]] | + | [[Category: Allingham JS]] |
| - | [[Category: Auria, M V.D]] | + | [[Category: D'Auria MV]] |
| - | [[Category: Rayment, I]] | + | [[Category: Rayment I]] |
| - | [[Category: Zampella, A]] | + | [[Category: Zampella A]] |
| - | [[Category: Actin]]
| + | |
| - | [[Category: Filament capping]]
| + | |
| - | [[Category: Filament severing]]
| + | |
| - | [[Category: Marine macrolide]]
| + | |
| - | [[Category: Sphinxolide b]]
| + | |
| - | [[Category: Structural protein]]
| + | |
| - | [[Category: Toxin]]
| + | |
| Structural highlights
Function
ACTS_RABIT Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Allingham JS, Zampella A, D'Auria MV, Rayment I. Structures of microfilament destabilizing toxins bound to actin provide insight into toxin design and activity. Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14527-32. Epub 2005 Sep 28. PMID:16192358 doi:0502089102
|
