{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:06:30Z","timestamp":1790651190840,"version":"4.1.0"},"reference-count":78,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"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":[[2013,9]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Monothiol glutaredoxins (1\n                    <jats:italic toggle=\"yes\">-<\/jats:italic>\n                    C\n                    <jats:italic toggle=\"yes\">-<\/jats:italic>\n                    Grxs) are small proteins linked to the cellular iron and redox metabolism.\n                    <jats:italic toggle=\"yes\">Trypanosoma brucei brucei<\/jats:italic>\n                    , model organism for human African trypanosomiasis, expresses three 1-C-Grxs. 1-C-Grx1 is a highly abundant mitochondrial protein capable to bind an iron\u2013sulfur cluster (ISC)\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    using glutathione (GSH) as cofactor. We here report on the functional and structural analysis of 1-C-Grx1 in relation to its ISC-binding properties.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    An N-terminal extension unique to 1-C-Grx1 from trypanosomatids affects the oligomeric structure and the ISC-binding capacity of the protein. The active-site Cys104 is essential for ISC binding, and the parasite-specific glutathionylspermidine and trypanothione can replace GSH as the ligands of the ISC. Interestingly, trypanothione forms stable protein-free ISC species that\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    are incorporated into the dithiol\n                    <jats:italic toggle=\"yes\">T. brucei<\/jats:italic>\n                    2-C-Grx1, but not 1-C-Grx1. Overexpression of the C104S mutant of 1-C-Grx1 impairs disease progression in a mouse model. The structure of the Grx-domain of 1-C-Grx1 was solved by nuclear magnetic resonance spectroscopy. Despite the fact that several residues\u2014which in other 1-C-Grxs are involved in the noncovalent binding of GSH\u2014are conserved, different physicochemical approaches did not reveal any specific interaction between 1-C-Grx1 and free thiol ligands.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation:<\/jats:italic>\n                    <\/jats:bold>\n                    Parasite Grxs are able to coordinate an ISC formed with trypanothione, suggesting a new mechanism of ISC binding and a novel function for the parasite-specific dithiol. The first 3D structure and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    relevance of a 1-C-Grx from a pathogenic protozoan are reported.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    <\/jats:bold>\n                    <jats:italic toggle=\"yes\">T. brucei<\/jats:italic>\n                    1-C-Grx1 is indispensable for mammalian parasitism and utilizes a new mechanism for ISC binding.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal<\/jats:italic>\n                    . 19, 665\u2013682.\n                  <\/jats:p>","DOI":"10.1089\/ars.2012.4859","type":"journal-article","created":{"date-parts":[[2012,12,24]],"date-time":"2012-12-24T05:28:24Z","timestamp":1356326904000},"page":"665-682","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":40,"title":["Iron\u2013Sulfur Cluster Binding by Mitochondrial Monothiol Glutaredoxin-1 of\n                    <i>Trypanosoma brucei<\/i>\n                    : Molecular Basis of Iron\u2013Sulfur Cluster Coordination and Relevance for Parasite Infectivity"],"prefix":"10.1177","volume":"19","author":[{"given":"Bruno","family":"Manta","sequence":"first","affiliation":[{"name":"Institut Pasteur de Montevideo","place":["Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Pavan","sequence":"additional","affiliation":[{"name":"Universit\u00e0 di Padova","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattia","family":"Sturlese","sequence":"additional","affiliation":[{"name":"Universit\u00e0 di Padova","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Montevideo","place":["Uruguay"]},{"name":"Universidad de la Rep\u00fablica","place":["Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Crispo","sequence":"additional","affiliation":[{"name":"Institut Pasteur de Montevideo","place":["Uruguay"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Berndt","sequence":"additional","affiliation":[{"name":"Heinrich Heine University D\u00fcsseldorf","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Luise","family":"Krauth-Siegel","sequence":"additional","affiliation":[{"name":"Heidelberg University","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Bellanda","sequence":"additional","affiliation":[{"name":"Universit\u00e0 di Padova","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo A.","family":"Comini","sequence":"additional","affiliation":[{"name":"Institut Pasteur de 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