{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T21:23:31Z","timestamp":1792531411828,"version":"4.5.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T00:00:00Z","timestamp":1705017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Plasmodium vivax<\/jats:italic> is the most widely distributed human malaria parasite. The eradication of vivax malaria remains challenging due to transmission of drug-resistant parasite and dormant liver form. Consequently, anti-malarial drugs with novel mechanisms of action are urgently demanded. Glucose uptake blocking strategy is suggested as a novel mode of action that leads to selective starvation in various species of malaria parasites. The role of hexose transporter 1 in <jats:italic>Plasmodium<\/jats:italic> species is glucose uptake, and its blocking strategies proved to successfully induce selective starvation. However, there is limited information on the glucose uptake properties via <jats:italic>P. vivax<\/jats:italic> hexose transporter 1 (PvHT1). Thus, we focused on the PvHT1 to precisely identify its properties of glucose uptake. The PvHT1 North Korean strain (PvHT1<jats:sub>NK<\/jats:sub>) expressed <jats:italic>Xenopus laevis<\/jats:italic> oocytes mediating the transport of [<jats:sup>3<\/jats:sup>H] deoxy-D-glucose (ddGlu) in an expression and incubation time-dependent manner without sodium dependency. Moreover, the PvHT1<jats:sub>NK<\/jats:sub> showed no exchange mode of glucose in efflux experiments and concentration-dependent results showed saturable kinetics following the Michaelis-Menten equation. Non-linear regression analysis revealed a Km value of 294.1 \u03bcM and a Vmax value of 1,060 pmol\/oocyte\/hr, and inhibition experiments showed a strong inhibitory effect by glucose, mannose, and ddGlu. Additionally, weak inhibition was observed with fructose and galactose. Comparison of amino acid sequence and tertiary structure between <jats:italic>P. falciparum<\/jats:italic> and <jats:italic>P. vivax<\/jats:italic> HT1 revealed a completely conserved residue in glucose binding pocket. This result supported that the glucose uptake properties are similar to <jats:italic>P. falciparum<\/jats:italic>, and PfHT1 inhibitor (compound 3361) works in <jats:italic>P. vivax<\/jats:italic>. These findings provide properties of glucose uptake via PvHT1<jats:sub>NK<\/jats:sub> for carbohydrate metabolism and support the approaches to vivax malaria drug development strategy targeting the PvHT1 for starving of the parasite.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1321240","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T04:38:30Z","timestamp":1705034310000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional characterization of Plasmodium vivax hexose transporter 1"],"prefix":"10.3389","volume":"13","author":[{"given":"Jeong Yeon","family":"Won","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Mazigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seok Ho","family":"Cha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hee","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"W252","DOI":"10.1093\/nar\/gku340","article-title":"SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information","volume":"42","author":"Biasini","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1096\/fj.10-173278","article-title":"A constitutive pan-hexose permease for the Plasmodium life cycle and transgenic models for screening of antimalarial sugar analogs","volume":"25","author":"Blume","year":"2011","journal-title":"FASEB J."},{"key":"B3","doi-asserted-by":"publisher","first-page":"16290","DOI":"10.1073\/pnas.0807404105","article-title":"The transcriptome of Plasmodium vivax reveals divergence and diversity of transcriptional regulation in malaria parasites","volume":"105","author":"Bozdech","year":"2008","journal-title":"Proc. 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