3BZ9

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

3BZ9 の概要

• エントリーDOI: 10.2210/pdb3bz9/pdb
• 関連するPDBエントリー: 1YV3 3BZ7 3BZ8
• 分子名称: Myosin-2 heavy chain, non muscle, MAGNESIUM ION, VANADATE ION, ... (7 entities in total)
• 機能のキーワード: myosin inhibitor, motor domain, blebbistatin analogue, actin-binding, atp-binding, calmodulin-binding, coiled coil, cytoplasm, methylation, motor protein, nucleotide-binding, phosphoprotein, contractile protein
• 由来する生物種: Dictyostelium discoideum
• 細胞内の位置: Cytoplasm, cell cortex: P08799
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 87678.23

構造登録者

Allingham, J.S.,Rayment, I. (登録日: 2008-01-17, 公開日: 2008-02-19, 最終更新日: 2023-08-30)

主引用文献

Lucas-Lopez, C.,Allingham, J.S.,Lebl, T.,Lawson, C.P.,Brenk, R.,Sellers, J.R.,Rayment, I.,Westwood, N.J.
The small molecule tool (S)-(-)-blebbistatin: novel insights of relevance to myosin inhibitor design.
Org.Biomol.Chem., 6:2076-2084, 2008

PubMed Abstract: 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.

PubMed: 18528569
DOI: 10.1039/b801223g

実験手法

X-RAY DIFFRACTION (2.1 Å)