Structural basis of Fusarium myosin I inhibition by phenamacril

Zhou, Yuxin; Zhou, X. Edward; Gong, Yuanping; Zhu, Yuanye; Cao, Xiaoman; Brunzelle, Joseph S.; Xu, H. Eric; Zhou, Mingguo; Melcher, Karsten; Zhang, Feng

doi:10.1371/journal.ppat.1008323

Structural basis of Fusarium myosin I inhibition by phenamacril

Journal Article · Thu Mar 12 00:00:00 EDT 2020 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1008323· OSTI ID:1627922

Zhou, Yuxin ^[1]; ^[2]; Gong, Yuanping ^[3]; ^[3]; Cao, Xiaoman ^[3]; Brunzelle, Joseph S. ^[4]; Xu, H. Eric ^[5]; Zhou, Mingguo ^[3]; ^[2]; ^[3]

Nanjing Agricultural Univ. of Technology (China). Key Lab. of Pesticide, College of Plant Protection; Van Andel Inst. (VARI), Grand Rapids, MI (United States). Center of Cancer and Cell Biology, Program for Structural Biology; DOE/OSTI
Van Andel Inst. (VARI), Grand Rapids, MI (United States). Center of Cancer and Cell Biology, Program for Structural Biology
Nanjing Agricultural Univ. of Technology (China). Key Lab. of Pesticide, College of Plant Protection
Northwestern Univ., Argonne, IL (United States). Synchrotron Research Center, Life Science Collaborative Access Team
Van Andel Inst. (VARI), Grand Rapids, MI (United States). Center of Cancer and Cell Biology, Program for Structural Biology; Chinese Academy of Sciences (CAS), Shanghai (China)

Fusarium is a genus of filamentous fungi that includes species that cause devastating diseases in major staple crops, such as wheat, maize, rice, and barley, resulting in severe yield losses and mycotoxin contamination of infected grains. Phenamacril is a novel fungicide that is considered environmentally benign due to its exceptional specificity; it inhibits the ATPase activity of the sole class I myosin of only a subset of Fusarium species including the major plant pathogens F. graminearum, F. asiaticum and F. fujikuroi. To understand the underlying mechanisms of inhibition, species specificity, and resistance mutations, we have determined the crystal structure of phenamacril-bound F. graminearum myosin I. Phenamacril binds in the actin-binding cleft in a new allosteric pocket that contains the central residue of the regulatory Switch 2 loop and that is collapsed in the structure of a myosin with closed actin-binding cleft, suggesting that pocket occupancy blocks cleft closure. We have further identified a single, transferable phenamacril-binding residue found exclusively in phenamacril-sensitive myosins to confer phenamacril selectivity.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC); Van Andel Research Institute; National Natural Science Foundation of China (NSFC); Fok Ying-Tong Education Foundation; Six Talent Peaks Project in Jiangsu Province

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1627922

Alternate ID(s):: OSTI ID: 1657604

Journal Information:: PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 3 Vol. 16; ISSN 1553-7374

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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