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[[Image:3bz8.jpg|left|200px]]
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{{STRUCTURE_3bz8|  PDB=3bz8  |  SCENE=  }}
'''Crystal Structures of (S)-(-)-Blebbistatin Analogs bound to Dictyostelium discoideum myosin II'''


==Crystal Structures of (S)-(-)-Blebbistatin Analogs bound to Dictyostelium discoideum myosin II==
<StructureSection load='3bz8' size='340' side='right'caption='[[3bz8]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bz8]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BZ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BZ8 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BL6:(3AS)-3A-HYDROXY-7-METHYL-1-PHENYL-1,2,3,3A-TETRAHYDRO-4H-PYRROLO[2,3-B]QUINOLIN-4-ONE'>BL6</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=VO4:VANADATE+ION'>VO4</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=3bz8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bz8 OCA], [https://pdbe.org/3bz8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bz8 RCSB], [https://www.ebi.ac.uk/pdbsum/3bz8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bz8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MYS2_DICDI MYS2_DICDI] Myosin is a protein that binds to actin and has ATPase activity that is activated by actin.
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bz/3bz8_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bz8 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The small molecule blebbistatin is now a front line tool in the study of myosin function. Chemical modification of the tricyclic core of blebbistatin could deliver the next generation of myosin inhibitors and to help address this we report here on the impact of structural changes in the methyl-substituted aromatic ring of blebbistatin on its biological activity. Chemical methods for the preparation of isomeric methyl-containing analogues are reported and a series of co-crystal structures are used to rationalise the observed variations in their biological activity. These studies further support the view that the previously identified binding mode of blebbistatin to Dictyostelium discoideum myosin II is of relevance to its mode of action. A discussion of the role that these observations have on planning the synthesis of focused libraries of blebbistatin analogues is also provided including an assessment of possibilities by computational methods. These studies are ultimately directed at the development of novel myosin inhibitors with improved affinity and different selectivity profiles from blebbistatin itself.


==Overview==
The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design.,Lucas-Lopez C, Allingham JS, Lebl T, Lawson CP, Brenk R, Sellers JR, Rayment I, Westwood NJ Org Biomol Chem. 2008 Jun 21;6(12):2076-84. Epub 2008 Apr 21. PMID:18528569<ref>PMID:18528569</ref>
The small molecule blebbistatin is now a front line tool in the study of myosin function. Chemical modification of the tricyclic core of blebbistatin could deliver the next generation of myosin inhibitors and to help address this we report here on the impact of structural changes in the methyl-substituted aromatic ring of blebbistatin on its biological activity. Chemical methods for the preparation of isomeric methyl-containing analogues are reported and a series of co-crystal structures are used to rationalise the observed variations in their biological activity. These studies further support the view that the previously identified binding mode of blebbistatin to Dictyostelium discoideum myosin II is of relevance to its mode of action. A discussion of the role that these observations have on planning the synthesis of focused libraries of blebbistatin analogues is also provided including an assessment of possibilities by computational methods. These studies are ultimately directed at the development of novel myosin inhibitors with improved affinity and different selectivity profiles from blebbistatin itself.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
3BZ8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Dictyostelium_discoideum Dictyostelium discoideum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BZ8 OCA].
</div>
<div class="pdbe-citations 3bz8" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design., Lucas-Lopez C, Allingham JS, Lebl T, Lawson CP, Brenk R, Sellers JR, Rayment I, Westwood NJ, Org Biomol Chem. 2008 Jun 21;6(12):2076-84. Epub 2008 Apr 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18528569 18528569]
*[[Myosin 3D Structures|Myosin 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Dictyostelium discoideum]]
[[Category: Dictyostelium discoideum]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Allingham, J S.]]
[[Category: Allingham JS]]
[[Category: Rayment, I.]]
[[Category: Rayment I]]
[[Category: Actin-binding]]
[[Category: Atp-binding]]
[[Category: Blebbistatin analogue]]
[[Category: Calmodulin-binding]]
[[Category: Coiled coil]]
[[Category: Contractile protein]]
[[Category: Cytoplasm]]
[[Category: Methylation]]
[[Category: Motor domain]]
[[Category: Motor protein]]
[[Category: Myosin inhibitor]]
[[Category: Nucleotide-binding]]
[[Category: Phosphoprotein]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 18 12:20:48 2008''

Latest revision as of 08:59, 13 August 2026

Crystal Structures of (S)-(-)-Blebbistatin Analogs bound to Dictyostelium discoideum myosin II

3bz8, resolution 2.20Å

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