3bz8
From Proteopedia
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==Overview== | ==Overview== | ||
| - | + | 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== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | The | + | 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] |
[[Category: Dictyostelium discoideum]] | [[Category: Dictyostelium discoideum]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Nucleotide-binding]] | [[Category: Nucleotide-binding]] | ||
[[Category: Phosphoprotein]] | [[Category: Phosphoprotein]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 18 12:20:48 2008'' |
Revision as of 09:20, 18 June 2008
Crystal Structures of (S)-(-)-Blebbistatin Analogs bound to Dictyostelium discoideum myosin II
Overview
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
3BZ8 is a Single protein structure of sequence from Dictyostelium discoideum. Full crystallographic information is available from OCA.
Reference
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 Page seeded by OCA on Wed Jun 18 12:20:48 2008
Categories: Dictyostelium discoideum | Single protein | Allingham, J S. | Rayment, I. | Actin-binding | Atp-binding | Blebbistatin analogue | Calmodulin-binding | Coiled coil | Contractile protein | Cytoplasm | Methylation | Motor domain | Motor protein | Myosin inhibitor | Nucleotide-binding | Phosphoprotein
