8CJ9

Crystal structure of maize CKO/CKX8 in complex with urea-derived inhibitor 2-[(3,5-dichlorophenyl)carbamoylamino]benzamide

Summary for 8CJ9

• Entry DOI: 10.2210/pdb8cj9/pdb
• Descriptor: cytokinin dehydrogenase, FLAVIN-ADENINE DINUCLEOTIDE, 2-[[3,5-bis(chloranyl)phenyl]carbamoylamino]benzamide, ... (6 entities in total)
• Functional Keywords: hormone degradation, flavoprotein
• Biological source: Zea mays
• Total number of polymer chains: 2
• Total formula weight: 120211.23

Authors

Kopecny, D.,Briozzo, P.,Morera, S. (deposition date: 2023-02-12, release date: 2024-02-21, Last modification date: 2024-10-23)

Primary citation

Nisler, J.,Klimes, P.,Koncitikova, R.,Kadlecova, A.,Voller, J.,Chalaki, M.,Karampelias, M.,Murvanidze, N.,Werbrouck, S.P.O.,Kopecny, D.,Havlicek, L.,De Diego, N.,Briozzo, P.,Morera, S.,Zalabak, D.,Spichal, L.
Cytokinin oxidase/dehydrogenase inhibitors: progress towards agricultural practice.
J.Exp.Bot., 75:4873-4890, 2024

PubMed Abstract: Cytokinin oxidase/dehydrogenase (CKX) inhibitors reduce the degradation of cytokinins in plants and thereby may improve the efficiency of agriculture and plant tissue culture-based practices. Here, we report a synthesis and structure-activity relationship study of novel urea derivatives concerning their CKX inhibitory activity. The best compounds showed sub-nanomolar IC50 values with maize ZmCKX1, the lowest value yet documented. Other CKX isoforms of maize (Zea mays) and Arabidopsis were also inhibited very effectively. The binding mode of four compounds was characterized based on high-resolution crystal complex structures. Using the soil nematode Caenorhabditis elegans, and human skin fibroblasts, key CKX inhibitors with low toxicity were identified. These compounds enhanced the shoot regeneration of Lobelia, Drosera, and Plectranthus, as well as the growth of Arabidopsis and Brassica napus. At the same time, a key compound (namely 82), activated a cytokinin primary response gene ARR5:GUS and cytokinin sensor TCSv2:GUS, without activating the Arabidopsis cytokinin receptors AHK3 and AHK4. This strongly implies that the effect of compound 82 is due to the upregulation of cytokinin signalling. Overall, this work presents highly effective and easily prepared CKX inhibitors with a low risk of environmental toxicity for further investigation of their potential in agriculture and biotechnology.

PubMed: 38776394
DOI: 10.1093/jxb/erae239

Experimental method

X-RAY DIFFRACTION (1.93 Å)