Legrand Pierre, Dumas Renaud, Seux Marlene, Rippert Pascal, Ravelli Raimond, Ferrer Jean-Luc, Matringe Michel
Institut de Biologie Structurale Jean-Pierre Ebel, Centre National de la Recherche Scientifique, Université Joseph Fourier, Laboratoire de Cristallographie et Cristallogenèse des Protéines/Groupe Synchrotron, 38027 Grenoble cedex 1, France.
Structure. 2006 Apr;14(4):767-76. doi: 10.1016/j.str.2006.01.006.
The extreme diversity in substrate specificity, and in the regulation mechanism of arogenate/prephenate dehydrogenase enzymes in nature, makes a comparative structural study of these enzymes of great interest. We report here on the biochemical and structural characterization of arogenate dehydrogenase from Synechocystis sp. (TyrAsy). This work paves the way for the understanding of the structural determinants leading to diversity in substrate specificity, and of the regulation mechanisms of arogenate/prephenate dehydrogenases. The overall structure of TyrAsy in complex with NADP was refined to 1.6 A. The asymmetric unit contains two TyrAsy homodimers, with each monomer consisting of a nucleotide binding N-terminal domain and a particularly unique alpha-helical C-terminal dimerization domain. The substrate arogenate was modeled into the active site. The model of the ternary complex enzyme-NADP-arogenate nicely reveals at the atomic level the concerted mechanism of the arogenate/prephenate dehydrogenase reaction.
自然界中，预苯酸脱氢酶在底物特异性和调控机制方面存在极大差异，这使得对这些酶进行比较结构研究极具意义。我们在此报告来自集胞藻属（TyrAsy）的预苯酸脱氢酶的生化和结构特征。这项工作为理解导致底物特异性多样性的结构决定因素以及预苯酸脱氢酶的调控机制铺平了道路。与NADP结合的TyrAsy的整体结构被精修至1.6埃。不对称单元包含两个TyrAsy同型二聚体，每个单体由一个核苷酸结合N端结构域和一个特别独特的α螺旋C端二聚化结构域组成。底物预苯酸被模拟到活性位点。酶-NADP-预苯酸三元复合物模型在原子水平上很好地揭示了预苯酸脱氢酶反应的协同机制。
