7C8L

Hybrid designing of potent inhibitors of Striga strigolactone receptor ShHTL7

7C8L の概要

• エントリーDOI: 10.2210/pdb7c8l/pdb
• 分子名称: Hyposensitive to light 7, 2-(2-{2-[2-(2-{2-[2-(2-{2-[4-(1,1,3,3-TETRAMETHYL-BUTYL)-PHENOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOX Y}-ETHOXY)-ETHANOL, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: shhtl7, kk1007, covalent inhibitor, specificity, striga, hydrolase
• 由来する生物種: Striga hermonthica (Purple witchweed)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31596.32

構造登録者

Shahul Hameed, U.F.,Arold, S.T. (登録日: 2020-06-02, 公開日: 2021-06-02, 最終更新日: 2024-10-30)

主引用文献

Zarban, R.A.,Hameed, U.F.S.,Jamil, M.,Ota, T.,Wang, J.Y.,Arold, S.T.,Asami, T.,Al-Babili, S.
Rational design of Striga hermonthica-specific seed germination inhibitors.
Plant Physiol., 188:1369-1384, 2022

PubMed Abstract: The obligate hemiparasitic weed Striga hermonthica grows on cereal roots and presents a severe threat to global food security by causing enormous yield losses, particularly in sub-Saharan Africa. The rapidly increasing Striga seed bank in infested soils provides a major obstacle in controlling this weed. Striga seeds require host-derived strigolactones (SLs) for germination, and corresponding antagonists could be used as germination inhibitors. Recently, we demonstrated that the common detergent Triton X-100 is a specific inhibitor of Striga seed germination by binding noncovalently to its receptor, S. hermonthica HYPO-SENSITIVE TO LIGHT 7 (ShHTL7), without blocking the rice (Oryza sativa) SL receptor DWARF14 (OsD14). Moreover, triazole ureas, the potent covalently binding antagonists of rice SL perception with much higher activity toward OsD14, showed inhibition of Striga but were less specific. Considering that Triton X-100 is not suitable for field application and by combining structural elements of Triton and triazole urea, we developed two hybrid compounds, KK023-N1 and KK023-N2, as potential Striga-specific germination inhibitors. Both compounds blocked the hydrolysis activity of ShHTL7 but did not affect that of OsD14. Binding of KK023-N1 diminished ShHTL7 interaction with S. hermonthica MORE AXILLARY BRANCHING 2, a major component in SL signal transduction, and increased ShHTL7 thermal specificity. Docking studies indicate that KK023-N1 binding is not covalent but is caused by hydrophobic interactions. Finally, in vitro and greenhouse tests revealed specific inhibition of Striga seed germination, which led to a 38% reduction in Striga infestation in pot experiments. These findings reveal that KK023-N1 is a potential candidate for combating Striga and a promising basis for rational design and development of further Striga-specific herbicides.

PubMed: 34850204
DOI: 10.1093/plphys/kiab547

実験手法

X-RAY DIFFRACTION (1.45 Å)