title: Direct and selective small-molecule inhibition of photosynthetic PEP carboxylase: New approach to combat C4 weeds in arable crops.
abstract: Phosphoenolpyruvate carboxylase (PEPC) is a key enzyme of C4 photosynthesis. Besides, non-photosynthetic isoforms of PEPC are found in bacteria and all types of plants, although not in animals or fungi. A single residue in the allosteric feedback inhibitor site of PEPC was shown to adjust the affinity of the photosynthetic and non-photosynthetic isoforms for feedback inhibition by metabolites of the C4 pathway. Here, we applied computational screening and biochemical analyses to identify molecules that selectively inhibit C4 PEPC, but have no effect on the activity of non-photosynthetic PEPCs. We found two types of selective inhibitors, catechins and quinoxalines. Binding constants in the lower μM range and a strong preference for C4 PEPC qualify the quinoxaline compounds as potential selective herbicides to combat C4 weeds.
authors.affiliation: Center of Excellence on Plant Sciences (CEPLAS), Institute of Biochemical Plant Physiology, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Judith Katharina
authors.initials: JK
authors.lastname: Paulus
authors.affiliation: Center of Excellence on Plant Sciences (CEPLAS), Institute of Biochemical Plant Physiology, Heinrich Heine University Düsseldorf, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Förster
authors.affiliation: Center of Excellence on Plant Sciences (CEPLAS), Institute of Biochemical Plant Physiology, Heinrich Heine University Düsseldorf, Germany. Electronic address: georg.groth@uni-duesseldorf.de.
authors.forename: Georg
authors.initials: G
authors.lastname: Groth
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D018556:Crops, Agricultural; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D010730:Phosphoenolpyruvate Carboxylase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010788:Photosynthesis / Q000187:drug effects*; D057685:Plant Weeds / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011487:Protein Conformation; D058728:Weed Control / Q000379:methods*
chemical_list: D004791:Enzyme Inhibitors; D010730:Phosphoenolpyruvate Carboxylase
keywords: C(4) photosynthesis; C(4) specific inhibitor; PEP carboxylase; Selective herbicide; Weed