{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:51:34Z","timestamp":1777434694846,"version":"3.51.4"},"reference-count":52,"publisher":"SAGE Publications","issue":"18","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      New drugs are needed to treat flatworm infections that cause severe human diseases such as schistosomiasis. The unique flatworm enzyme thioredoxin glutathione reductase (TGR), structurally different from the human enzyme, is a key drug target. Structural studies of the flatworm\n                      <jats:italic toggle=\"yes\">Echinococcus granulosus<\/jats:italic>\n                      TGR, free and complexed with Au\n                      <jats:sup>I<\/jats:sup>\n                      -MPO, a novel gold inhibitor, together with inhibition assays were performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Au\n                      <jats:sup>I<\/jats:sup>\n                      -MPO is a potent TGR inhibitor that achieves 75% inhibition at a 1:1 TGR:Au ratio and efficiently kills\n                      <jats:italic toggle=\"yes\">E. granulosus in vitro<\/jats:italic>\n                      . The structures revealed salient insights: (i) unique monomer\u2013monomer interactions, (ii) distinct binding sites for thioredoxin and the glutaredoxin (Grx) domain, (iii) a single glutathione disulfide reduction site in the Grx domain, (iv) rotation of the Grx domain toward the Sec-containing redox active site, and (v) a single gold atom bound to Cys\n                      <jats:sup>519<\/jats:sup>\n                      and Cys\n                      <jats:sup>573<\/jats:sup>\n                      in the Au\n                      <jats:sup>I<\/jats:sup>\n                      -TGR complex. Structural modeling suggests that these residues are involved in the stabilization of the Sec-containing C-terminus. Consistently, Cys\u2192Ser mutations in these residues decreased TGR activities. Mass spectroscopy confirmed these cysteines are the primary binding site.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation:<\/jats:title>\n                    <jats:p>The identification of a primary site for gold binding and the structural model provide a basis for gold compound optimization through scaffold adjustments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      The structural study revealed that TGR functions are achieved not only through a mobile Sec-containing redox center but also by rotation of the Grx domain and distinct binding sites for Grx domain and thioredoxin. The conserved Cys\n                      <jats:sup>519<\/jats:sup>\n                      and Cys\n                      <jats:sup>573<\/jats:sup>\n                      residues targeted by gold assist catalysis through stabilization of the Sec-containing redox center.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                      . 27, 1491\u20131504.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2016.6816","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T15:03:21Z","timestamp":1493737401000},"page":"1491-1504","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["The Enzymatic and Structural Basis for Inhibition of\n                    <i>Echinococcus granulosus<\/i>\n                    Thioredoxin Glutathione Reductase by Gold(I)"],"prefix":"10.1177","volume":"27","author":[{"given":"Gustavo","family":"Salinas","sequence":"first","affiliation":[{"name":"Institut Pasteur de Montevideo","place":["Uruguay"]},{"name":"Universidad de la Rep\u00fablica","place":["Uruguay"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"National Jewish Health"},{"name":"University of Colorado Denver"},{"name":"Beijing Forestry University","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"National Jewish Health"},{"name":"University of Colorado Denver"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Bonilla","sequence":"additional","affiliation":[{"name":"Universidad de la Rep\u00fablica","place":["Uruguay"]},{"name":"Institut Pasteur de Montevideo","place":["Uruguay"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Yu","sequence":"additional","affiliation":[{"name":"National Jewish Health"},{"name":"University of Colorado Denver"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Novikov","sequence":"additional","affiliation":[{"name":"National Jewish Health"},{"name":"University of Colorado Denver"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veridiana G.","family":"Virginio","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio Grande do Sul","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrique B.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universidade Federal do Rio Grande do Sul","place":["Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisol","family":"Vieites","sequence":"additional","affiliation":[{"name":"Universidad de la Rep\u00fablica","place":["Uruguay"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vadim N.","family":"Gladyshev","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinorah","family":"Gambino","sequence":"additional","affiliation":[{"name":"Universidad de la Rep\u00fablica","place":["Uruguay"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaodong","family":"Dai","sequence":"additional","affiliation":[{"name":"National Jewish Health"},{"name":"University of Colorado Denver"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2017,12,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209266200"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(02)00108-X"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.141960"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21986"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.020701"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3085"},{"key":"e_1_3_3_8_2","first-page":"226","volume-title":"Methods in Enzymology","author":"Arner ESJ","year":"1999","unstructured":"Arner ESJ, , Zhong L, , and Holmgren A. 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