Screening of protonstatin-1 (PS-1) analogs for improved inhibitors of plant plasma membrane H+-ATPase activity

Yongqing Yang; Xiaohui Liu; Xin Wang; Wanjia Lv; Xiao Liu; Liang Ma; Haiqi Fu; Shu Song; Xiaoguang Lei

doi:10.3389/fpls.2022.973471

Screening of protonstatin-1 (PS-1) analogs for improved inhibitors of plant plasma membrane H⁺-ATPase activity

Front Plant Sci. 2022 Oct 12:13:973471. doi: 10.3389/fpls.2022.973471. eCollection 2022.

Authors

Yongqing Yang¹, Xiaohui Liu², Xin Wang², Wanjia Lv¹, Xiao Liu¹, Liang Ma¹, Haiqi Fu¹, Shu Song¹, Xiaoguang Lei²

Affiliations

¹ College of Biological Sciences, China Agricultural University, Beijing, China.
² Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.

Abstract

We previously identified protonstatin-1 (PS-1) as a selective inhibitor of plasma membrane H⁺-ATPase (PM H⁺-ATPase) activity and used it as a tool to validate the chemiosmotic model for polar auxin transport. Here, to obtain compounds with higher affinity than PS-1 for PM H⁺-ATPase, we synthesized 34 PS-1 analogs and examined their ability to inhibit PM H⁺-ATPase activity. The 34 analogs showed varying inhibitory effects on the activity of this enzyme. The strongest effect was observed for the small molecule PS-2, which was approximately five times stronger than PS-1. Compared to PS-1, PS-2 was also a stronger inhibitor of auxin uptake as well as acropetal and basipetal polar auxin transport in Arabidopsis thaliana seedlings. Because PS-2 is a more potent inhibitor of PM H⁺-ATPase than PS-1, we believe that this compound could be used as a tool to study the functions of this key plant enzyme.

Keywords: PS-2; arabidopsis; auxin transport; inhibitor; plasma membrane H+-ATPase.