对mDia介导的肌动蛋白组装进行亚型选择性化学抑制。
Isoform-selective chemical inhibition of mDia-mediated actin assembly.
作者信息
Gauvin Timothy J, Fukui Jami, Peterson Jeffrey R, Higgs Henry N
机构信息
Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
出版信息
Biochemistry. 2009 Oct 13;48(40):9327-9. doi: 10.1021/bi901354z.
Abstract
Formins are potent actin assembly factors. Diaphanous formins, including mDia1, mDia2, and mDia3 in mammals, are implicated in mitosis and cytokinesis, but no chemical interactors have been reported. We developed an in vitro screen for inhibitors of actin assembly by mDia1 and identified an inhibitor of mDia1 and mDia2 that does not inhibit mDia3 at the concentrations tested. These results establish the druggability of mDia formins and introduce a first-generation inhibitor.
摘要
formin蛋白是强大的肌动蛋白组装因子。包括哺乳动物中的mDia1、mDia2和mDia3在内的透明质酸formin蛋白与有丝分裂和胞质分裂有关，但尚未有化学相互作用分子的报道。我们开发了一种体外筛选方法来筛选mDia1介导的肌动蛋白组装抑制剂，并鉴定出一种mDia1和mDia2的抑制剂，在所测试的浓度下不抑制mDia3。这些结果证实了mDia formin蛋白的可成药性，并引入了第一代抑制剂。
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