title: Molecular mechanisms in the selective basal activation of pyrabactin receptor 1: Comparative analysis of mutants.
abstract: 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.
authors.affiliation: National Research Council of Canada, Edmonton, Alberta, Canada ; Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Lyudmyla
authors.initials: L
authors.lastname: Dorosh
authors.affiliation: National Research Council of Canada, Saskatoon, Saskatchewan, Canada.
authors.forename: Nandhakishore
authors.initials: N
authors.lastname: Rajagopalan
authors.affiliation: National Research Council of Canada, Saskatoon, Saskatchewan, Canada ; Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Michele C
authors.initials: MC
authors.lastname: Loewen
authors.affiliation: National Research Council of Canada, Edmonton, Alberta, Canada ; Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Stepanova
keywords: ABA, A8S abscisic acid; Abscisic acid signaling; CA, constitutively active; Constitutively active mutations; ECD, essential collective dynamics; Essential collective dynamics analysis; HAB1, homology to ABA insensitive 1; MD, molecular dynamics; Molecular dynamics simulations; P2M, N-(pyridin-2-ylmethyl) naphthalene-1-sulfonamide or C16H14N2O2S; PCA, principal component analysis; PDB, Protein Data Bank; PP2C, phosphatase type 2C; PYL, PYR1-like; PYR1, pyrabactin resistance 1; PYV, pyrabactin or C16H13BrN2O2S; Pyrabactin resistance; RCAR, regulatory component of ABA response; WT, wild type