Minges Alexander, Groth Georg
Cluster of Excellence on Plant Sciences (CEPLAS), Institute of Biochemical Plant Physiology, Heinrich Heine University Düsseldorf, 40204 Düsseldorf, Germany.
PLoS One. 2017 Jul 10;12(7):e0181139. doi: 10.1371/journal.pone.0181139. eCollection 2017.
Pyruvate phosphate dikinase (PPDK) is an essential enzyme of C4 photosynthesis in plants, catalyzing the ATP-driven conversion of pyruvate to phosphoenolpyruvate (PEP). It is further used by some bacteria and unicellular protists in the reverse, ATP-forming direction. Many weed species use C4 photosynthesis in contrast to world's major crops, which are C3 plants. Hence inhibitors of PPDK may be used as C4-specific herbicides. By screening a library of 80 commercially available kinase inhibitors, we identified compounds derived from bisindolylmaleimide (bisindolylmaleimide IV, IC50 = 0.76 ± 0.13 μM) and indirubin (indirubin-3'-monoxime, IC50 = 4.2 ± 0.9 μM) that showed high inhibitory potency towards PPDK and are among the most effective PPDK inhibitors described today. Physiological studies on leaf tissues of a C4 model plant confirmed in vivo inhibition of C4-driven photosynthesis by these substances. Moreover, comparative docking studies of non-inhibitory bisindolylmaleimide derivatives suggest that the selectivity towards PPDK may be increased by addition of functional groups to the core structure.
丙酮酸磷酸双激酶（PPDK）是植物C4光合作用中的一种关键酶，催化由ATP驱动的丙酮酸向磷酸烯醇式丙酮酸（PEP）的转化。一些细菌和单细胞原生生物则以相反的方向利用它来生成ATP。与世界上主要的C3作物不同，许多杂草物种采用C4光合作用。因此，PPDK抑制剂可用作C4特异性除草剂。通过筛选80种市售激酶抑制剂库，我们鉴定出了源自双吲哚基马来酰亚胺（双吲哚基马来酰亚胺IV，IC50 = 0.76±0.13 μM）和靛玉红（靛玉红-3'-单肟，IC50 = 4.2±0.9 μM）的化合物，这些化合物对PPDK表现出高抑制活性，是目前报道的最有效的PPDK抑制剂之一。对一种C4模式植物叶片组织的生理学研究证实了这些物质在体内对C4驱动的光合作用的抑制作用。此外，对非抑制性双吲哚基马来酰亚胺衍生物的比较对接研究表明，通过在核心结构上添加官能团，对PPDK的选择性可能会提高。
