{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:13:34Z","timestamp":1768562014509,"version":"3.49.0"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,11,4]],"date-time":"2014-11-04T00:00:00Z","timestamp":1415059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The glycerol kinase (<jats:styled-content style=\"fixed-case\">GK<\/jats:styled-content>) of <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>frican human trypanosomes is compartmentalized in their glycosomes. Unlike the host <jats:styled-content style=\"fixed-case\">GK<\/jats:styled-content>, which under physiological conditions catalyzes only the forward reaction (<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\u2010dependent glycerol phosphorylation), trypanosome <jats:styled-content style=\"fixed-case\">GK<\/jats:styled-content> can additionally catalyze the reverse reaction. In fact, owing to this unique reverse catalysis, <jats:styled-content style=\"fixed-case\">GK<\/jats:styled-content> is potentially essential for the parasites survival in the human host, hence a promising drug target. The mechanism of its reverse catalysis was unknown; therefore, it was not clear if this ability was purely due to its localization in the organelles or whether structure\u2010based catalytic differences also contribute. To investigate this lack of information, the <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010ray crystal structure of this protein was determined up to 1.90\u2009\u00c5 resolution, in its unligated form and in complex with three natural ligands. These data, in conjunction with results from structure\u2010guided mutagenesis suggests that the trypanosome <jats:styled-content style=\"fixed-case\">GK<\/jats:styled-content> is possibly a transiently autophosphorylating threonine kinase, with the catalytic site formed by non\u2010conserved residues. Our results provide a series of structural peculiarities of this enzyme, and gives unexpected insight into the reverse catalysis mechanism. Together, they provide an encouraging molecular framework for the development of trypanosome <jats:styled-content style=\"fixed-case\">GK<\/jats:styled-content>\u2010specific inhibitors, which may lead to the design of new and safer trypanocidal drug(s).<\/jats:p>","DOI":"10.1111\/mmi.12831","type":"journal-article","created":{"date-parts":[[2014,10,15]],"date-time":"2014-10-15T07:38:36Z","timestamp":1413358716000},"page":"1315-1329","source":"Crossref","is-referenced-by-count":16,"title":["Molecular basis for the reverse reaction of <scp>A<\/scp>frican human trypanosomes glycerol kinase"],"prefix":"10.1111","volume":"94","author":[{"given":"Emmanuel Oluwadare","family":"Balogun","sequence":"first","affiliation":[{"name":"Department of Applied Biology Graduate School of Science and Technology Kyoto Institute of Technology  Sakyo\u2010ku Kyoto 606\u20108585 Japan"},{"name":"Department of Biomedical Chemistry Graduate School of Medicine The University of Tokyo  7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20100033 Japan"},{"name":"Department of Biochemistry Ahmadu Bello University  Zaria 2222 Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Ken","family":"Inaoka","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry Graduate School of Medicine The University of Tokyo  7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20100033 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoo","family":"Shiba","sequence":"additional","affiliation":[{"name":"Department of Applied Biology Graduate School of Science and Technology Kyoto Institute of Technology  Sakyo\u2010ku Kyoto 606\u20108585 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasutoshi","family":"Kido","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry Graduate School of Medicine The University of Tokyo  7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20100033 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiaki","family":"Tsuge","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry Graduate School of Medicine The University of Tokyo  7\u20103\u20101 Hongo Bunkyo\u2010ku Tokyo 113\u20100033 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Nara","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Parasitology Juntendo University School of Medicine  Tokyo 113\u20108421 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Parasitology Juntendo University School of Medicine  Tokyo 113\u20108421 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruki","family":"Honma","sequence":"additional","affiliation":[{"name":"Systems and Structural Biology Center RIKEN  Tsurumi Yokohama 230\u20100045 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Systems and Structural Biology Center RIKEN  Tsurumi Yokohama 230\u20100045 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences The University of Tokyo  Tokyo 113\u20100033 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences The University of Tokyo  Tokyo 113\u20100033 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A. 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