PDF(Pubmed)
Abstract：
Halo blight is a plant disease that leads to a significant decrease in the yield of common bean crops and kiwi fruits. The infection is caused by Pseudomonas syringae pathovars that produce phaseolotoxin, an antimetabolite which targets arginine metabolism, particularly by inhibition of ornithine transcarbamylase (OTC). OTC is responsible for production of citrulline from ornithine and carbamoyl phosphate. Here we present the first crystal structures of the plant OTC from Arabidopsis thaliana (AtOTC). Structural analysis of AtOTC complexed with ornithine and carbamoyl phosphate reveals that OTC undergoes a significant structural transition when ornithine enters the active site, from the opened to the closed state. In this study we discuss the mode of OTC inhibition by phaseolotoxin, which seems to be able to act only on the fully opened active site. Once the toxin is proteolytically cleaved, it mimics the reaction transition state analogue to fit inside the fully closed active site of OTC. Additionally, we indicate the differences around the gate loop region which rationally explain the resistance of some bacterial OTCs to phaseolotoxin.
摘要：
Halo疫病是一种植物病害，可导致普通豆类作物和猕猴桃的产量显着下降。感染是由丁香假单胞菌引起的，一种针对精氨酸代谢的抗代谢物，特别是通过抑制鸟氨酸转碳淀粉酶(OTC)。OTC负责从鸟氨酸和氨基甲酰磷酸生产瓜氨酸。在这里，我们介绍了来自拟南芥（AtOTC）的植物OTC的第一个晶体结构。与鸟氨酸和氨基甲酰磷酸酯络合的AtOTC的结构分析表明，当鸟氨酸进入活性位点时，OTC经历了显着的结构转变，从打开状态到关闭状态。在这项研究中，我们讨论了类毒素抑制OTC的模式，这似乎只能在完全开放的活动网站上采取行动。一旦毒素被蛋白水解裂解，它模拟反应过渡态类似物，以适应OTC完全封闭的活性位点。此外,我们指出了门环区域周围的差异，这些差异合理地解释了某些细菌OTC对phaseolotoxin的抗性。
