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JHAMT thus represents a promising molecular target for pest control, although the structural properties of canonical JHAMT remain uncharacterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Herein, we present the canonical JHAMT of\n                      <jats:italic>T. castaneum<\/jats:italic>\n                      ,\n                      <jats:italic>Tc<\/jats:italic>\n                      JHAMT3, and report its three\u2010dimensional structure at 2.50\u2009\u00c5 resolution.\n                      <jats:italic>Tc<\/jats:italic>\n                      JHAMT3 exhibits a conserved structural pattern with insect JHAMT homologs, consisting of one Rossmann fold domain and one substrate\u2010binding domain. Structural and biochemical analyses revealed that the insertion of four to six amino acids and the formation of the \u03b27\u2032 strand in\n                      <jats:italic>Tc<\/jats:italic>\n                      JHAMT3 constitute critical structural determinants underlying the methyltransferase activity of canonical JHAMTs. Furthermore, a novel JHAMT\u2010targeting inhibitor, JI3, was identified through structure\u2010based screening and inhibitory analyses, and it can effectively disrupt the development and metamorphosis processes of\n                      <jats:italic>T. castaneum<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Structural and biochemical analyses enabled the definition of the molecular basis for understanding the catalytic activity of canonical JHAMT. Additionally, the findings from this work provide a blueprint for the development of more potent specific inhibitors of JHAMT and present a novel lead compound for management and control of\n                      <jats:italic>T. castaneum<\/jats:italic>\n                      . \u00a9 2025 Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ps.70267","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T04:10:28Z","timestamp":1760760628000},"page":"1090-1099","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Unveiling the molecular architecture of\n                    <scp>\n                      <i>Tc<\/i>\n                      JHAMT\n                    <\/scp>\n                    : structural basis for catalytic efficiency and targeted inhibitor screening in the red flour beetle,\n                    <i>Tribolium 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