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Title: Structural basis of Fusarium myosin I inhibition by phenamacril

Journal Article · · PLoS Pathogens
 [1]; ORCiD logo [2];  [3]; ORCiD logo [3];  [3];  [4];  [5];  [3]; ORCiD logo [2]; ORCiD logo [3]
  1. 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
  2. Van Andel Inst. (VARI), Grand Rapids, MI (United States). Center of Cancer and Cell Biology, Program for Structural Biology
  3. Nanjing Agricultural Univ. of Technology (China). Key Lab. of Pesticide, College of Plant Protection
  4. Northwestern Univ., Argonne, IL (United States). Synchrotron Research Center, Life Science Collaborative Access Team
  5. 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.

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
Journal Information:
PLoS Pathogens, Vol. 16, Issue 3; ISSN 1553-7374
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 17 works
Citation information provided by
Web of Science

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Structure of myosin-1c tail bound to calmodulin provides insights into calcium-mediated conformational coupling journal December 2014
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