National Research Council of Canada, Edmonton, Alberta, Canada ; Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada.
National Research Council of Canada, Saskatoon, Saskatchewan, Canada.
FEBS Open Bio. 2014 May 21;4:496-509. doi: 10.1016/j.fob.2014.05.001. eCollection 2014.
Pyrabactin receptors (PYR) play a central role in abscisic acid (ABA) signal transduction; they are ABA receptors that inhibit type 2C protein phosphatases (PP2C). Molecular aspects contributing to increased basal activity of PYR against PP2C are studied by molecular dynamics (MD) simulations. An extensive series of MD simulations of the apo-form of mutagenized PYR1 as a homodimer and in complex with homology to ABA-insensitive 1 (HAB1) phosphatase are reported. In order to investigate the detailed molecular mechanisms mediating PYR1 activity, the MD data was analyzed by essential collective dynamics (ECD), a novel approach that allows the identification, with atomic resolution, of persistent dynamic correlations based on relatively short MD trajectories. Employing the ECD method, the effects of select mutations on the structure and dynamics of the PYR1 complexes were investigated and considered in the context of experimentally determined constitutive activities against HAB1. Approaches to rationally design constitutively active PYR1 constructs to increase PP2C inhibition are discussed.
吡喃并哒嗪受体（PYR）在脱落酸（ABA）信号转导中发挥核心作用；它们是抑制型 2C 蛋白磷酸酶（PP2C）的 ABA 受体。通过分子动力学（MD）模拟研究了导致 PYR 对 PP2C 的基础活性增加的分子方面。本文报道了一系列广泛的 apo 形式突变 PYR1 同源二聚体和与 ABA 不敏感 1（HAB1）磷酸酶同源复合物的 MD 模拟。为了研究介导 PYR1 活性的详细分子机制，通过基本集体动力学（ECD）对 MD 数据进行了分析，ECD 是一种新方法，可以基于相对较短的 MD 轨迹，以原子分辨率识别持久的动态相关性。利用 ECD 方法，研究了特定突变对 PYR1 复合物结构和动力学的影响，并结合实验测定的对 HAB1 的组成活性进行了考虑。讨论了合理设计组成型激活的 PYR1 构建体以增加 PP2C 抑制的方法。
