{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:21:05Z","timestamp":1791238865723,"version":"4.1.0"},"reference-count":34,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,6,15]]},"abstract":"<jats:p>The survival of malaria parasites in human RBCs (red blood cells) depends on the pentose phosphate pathway, both in Plasmodium falciparum and its human host. G6PD (glucose-6-phosphate dehydrogenase) deficiency, the most common human enzyme deficiency, leads to a lack of NADPH in erythrocytes, and protects from malaria. In P. falciparum, G6PD is combined with the second enzyme of the pentose phosphate pathway to create a unique bifunctional enzyme named GluPho (glucose-6-phosphate dehydrogenase\u20136-phosphogluconolactonase). In the present paper, we report for the first time the cloning, heterologous overexpression, purification and kinetic characterization of both enzymatic activities of full-length PfGluPho (P. falciparum GluPho), and demonstrate striking structural and functional differences with the human enzymes. Detailed kinetic analyses indicate that PfGluPho functions on the basis of a rapid equilibrium random Bi Bi mechanism, where the binding of the second substrate depends on the first substrate. We furthermore show that PfGluPho is inhibited by S-glutathionylation. The availability of recombinant PfGluPho and the major differences to hG6PD (human G6PD) facilitate studies on PfGluPho as an excellent drug target candidate in the search for new antimalarial drugs.<\/jats:p>","DOI":"10.1042\/bj20110170","type":"journal-article","created":{"date-parts":[[2011,5,27]],"date-time":"2011-05-27T15:11:02Z","timestamp":1306509062000},"page":"641-650","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Glucose-6-phosphate dehydrogenase\u20136-phosphogluconolactonase: a unique bifunctional enzyme from <i>Plasmodium falciparum<\/i>"],"prefix":"10.1042","volume":"436","author":[{"given":"Esther","family":"Jortzik","sequence":"first","affiliation":[{"name":"Interdisciplinary Research Center, Justus Liebig University, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boniface\u00a0M.","family":"Mailu","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center, Justus Liebig University, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"Preuss","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center, Justus Liebig University, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany"},{"name":"Department of Pediatrics, University of California San Diego, 200 West Arbor Drive, San Diego, CA 92103-8450, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Fischer","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center, Justus Liebig University, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bode","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Diego, 200 West Arbor Drive, San Diego, CA 92103-8450, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Rahlfs","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center, Justus Liebig University, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Becker","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center, Justus Liebig University, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2011,5,27]]},"reference":[{"key":"2021112214551151000_B1","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s001090050253","article-title":"Glucose-6-phosphate dehydrogenase deficiency and malaria","volume":"76","author":"Ruwende","year":"1998","journal-title":"J. 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Parasitol."},{"key":"2021112214551151000_B10","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1046\/j.1432-1327.2001.02078.x","article-title":"Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase. A novel bifunctional enzyme in malaria parasites","volume":"268","author":"Clarke","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"2021112214551151000_B11","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1046\/j.1365-2958.1997.2621629.x","article-title":"Plasmodium falciparum glucose-6-phosphate dehydrogenase (G6PD): the N-terminal portion is homologous to a predicted protein encoded near to G6PD in Haemophilus influenzae","volume":"23","author":"Scopes","year":"1997","journal-title":"Mol. 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Haematol."},{"key":"2021112214551151000_B21","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0166-6851(88)90144-2","article-title":"Glucose-6-phosphate dehydrogenase activity of the malaria parasite Plasmodium falciparum","volume":"31","author":"Ling","year":"1988","journal-title":"Mol. Biochem. Parasitol."},{"key":"2021112214551151000_B22","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/0022-2836(72)90101-5","article-title":"Human erythrocyte glucose 6-phosphate dehydrogenase: electron microscope studies on structure and interconversion of tetramers, dimers and monomers","volume":"68","author":"Wrigley","year":"1972","journal-title":"J. Mol. Biol."},{"key":"2021112214551151000_B23","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0167-4838(89)90004-6","article-title":"Kinetics of human erythrocyte glucose-6-phosphate dehydrogenase dimers","volume":"999","author":"Birke","year":"1989","journal-title":"Biochim. Biophys. 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Biol. Chem."},{"key":"2021112214551151000_B27","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1046\/j.1432-1033.2002.03015.x","article-title":"Recombinant human glucose-6-phosphate dehydrogenase. Evidence for a rapid-equilibrium random-order mechanism","volume":"269","author":"Wang","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"2021112214551151000_B28","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/0300-9084(91)90006-M","article-title":"Kinetic properties of normal human erythrocyte glucose-6-phosphate dehydrogenase dimers","volume":"73","author":"Adediran","year":"1991","journal-title":"Biochimie"},{"key":"2021112214551151000_B29","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1432-1033.1983.tb07442.x","article-title":"6-Phosphogluconolactonase purification, properties and activities in various tissues","volume":"133","author":"Bauer","year":"1983","journal-title":"Eur. J. 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