{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T10:59:23Z","timestamp":1780138763173,"version":"3.54.0"},"reference-count":60,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,13]],"date-time":"2023-08-13T00:00:00Z","timestamp":1691884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Foundation","award":["BE1540\/23-2"],"award-info":[{"award-number":["BE1540\/23-2"]}]},{"name":"German Research Foundation","award":["E3"],"award-info":[{"award-number":["E3"]}]},{"name":"LOEWE Center DRUID","award":["BE1540\/23-2"],"award-info":[{"award-number":["BE1540\/23-2"]}]},{"name":"LOEWE Center DRUID","award":["E3"],"award-info":[{"award-number":["E3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The protozoan parasite Plasmodium falciparum is the causative pathogen of the most severe form of malaria, for which novel strategies for treatment are urgently required. The primary energy supply for intraerythrocytic stages of Plasmodium is the production of ATP via glycolysis. Due to the parasite\u2019s strong dependence on this pathway and the significant structural differences of its glycolytic enzymes compared to its human counterpart, glycolysis is considered a potential drug target. In this study, we provide the first three-dimensional protein structure of P.\u00a0falciparum hexokinase (PfHK) containing novel information about the mechanisms of PfHK. We identified for the first time a Plasmodium-specific insertion that lines the active site. Moreover, we propose that this insertion plays a role in ATP binding. Residues of the insertion further seem to affect the tetrameric interface and therefore suggest a special way of communication among the different monomers. In addition, we confirmed that PfHK is targeted and affected by oxidative posttranslational modifications (oxPTMs). Both S-glutathionylation and S-nitrosation revealed an inhibitory effect on the enzymatic activity of PfHK.<\/jats:p>","DOI":"10.3390\/ijms241612739","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:13:57Z","timestamp":1692008037000},"page":"12739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Structural Analysis of Plasmodium falciparum Hexokinase Provides Novel Information about Catalysis Due to a Plasmodium-Specific Insertion"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4298-6889","authenticated-orcid":false,"given":"Melissa","family":"Dillenberger","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9316-0227","authenticated-orcid":false,"given":"Anke-Dorothee","family":"Werner","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Marburg, Hans-Meerwein-Str. 2, D-35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Sophie","family":"Velten","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Rahlfs","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Becker","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4422-6795","authenticated-orcid":false,"given":"Karin","family":"Fritz-Wolf","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University, D-35392 Giessen, Germany"},{"name":"Max-Planck Institute for Medical Research, Jahnstr. 29, D-69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,13]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022). 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