Phenylureas binding sites

Use of 3(3-azido-4 chlorophenyl)-1,1-dimethylurea (azidomonuron), a photoaffinity labelling analogue of the herbicidal phenylurea 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), has revealed Tyr 237 and Tyr 254 of D1 to be close to the herbicide binding site (1). An interesting property of DCMU is its ability, under certain conditions, to displace a bicarbonate ion which normally binds to PS2 in the region of the non-heme ferrous atom situated between and Qg. 

Certain substituted urea compounds, such as phenylurea or thidiazuron. Fig. (1), are very effective in the replacement of adenine-based cytokinins in promoting callus growth and other bioassays [27,28]. Molecular modeling revealed that the energetically optimal conformation of active urea derivatives have similar geometry as the isoprenoid side chain, so they can bind to the active sites of cytokinin metabolic enzymes and/or activate cytokinin receptors [29]. Thus, these compounds are likely to enhance their cytokinin effect by simultaneous activation of the receptor and inhibition of some of the cytokinin deactivating enzymes [11,30]. 

Whereas inhibition of chloroplast electron transport has been correlated with binding to a protein(s), the sites and mechanisms through which herbicides interfere with mitochondrial and chloroplast mediated phosphorylations remain to be identified. When lipophilic herbicides partition into the lipid phases of membranes, they could perturb lipid-lipid, lipid-protein, and protein-protein interactions that are required for membrane functions such as electron transport, ATP formation, and active transport. Evidence for general membrane perturbations caused by chlorpropham, 2,6-dinitroanilines, perfluidone, and certain phenylureas have been reported previously (8-11). 

The competitive binding experiments of Tischer and Strotmann (4) suggest that the phenylureas, biscarbamates, triazines, tria-zinones, and pyridazinones inhibit electron transport by interaction with the same component of PS II. Action at this site seemed to account for the phytotoxicity of pyrazon [5-amino-4-chloro-2-phenyl-3(2H)-pyridazinone]. In addition to action at this site, compounds with molecular substitutions onto the structure of pyrazon (Figure 1) also interfere with the formation of chloroplast membrane lipids, namely the chlorophylls, carotenoids, and glycerolipids. 

Pertinently substituted -triazines are known to inhibit PS II electron flow in chloroplasts and are herbicidal [20], and also phenylurea and carbamate herbicides are known to act at the same site as that of 5 -triazines [17]. In other words, they are bioisosters to each other with respect to the binding to the action site, or the bioisosterism between them is fairly high, irrespective of the apparently different structures. Moreover, phenylureas are known to have cytokinin activity [4,6]. Thus, the carbamates are expected to behave bioisosterically to phenylureas or 5 -triazines with respect to the interaction with the cytokinion receptor. 

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