{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:35:51Z","timestamp":1793763351579,"version":"4.6.1"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"29","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM118090"],"award-info":[{"award-number":["R35GM118090"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA235760"],"award-info":[{"award-number":["R01CA235760"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,7,19]]},"abstract":"<jats:p>\n                    Human glucose-6-phosphate dehydrogenase (G6PD) is the main cellular source of NADPH, and thus plays a key role in maintaining reduced glutathione to protect cells from oxidative stress disorders such as hemolytic anemia. G6PD is a multimeric enzyme that uses the cofactors \u03b2-D-glucose 6-phosphate (G6P) and \u201ccatalytic\u201d NADP\n                    <jats:sup>+<\/jats:sup>\n                    (NADP\n                    <jats:sup>+<\/jats:sup>\n                    c), as well as a \u201cstructural\u201d NADP\n                    <jats:sup>+<\/jats:sup>\n                    (NADP\n                    <jats:sup>+<\/jats:sup>\n                    s) located \u223c25 \u00c5 from the active site, to generate NADPH. While X-ray crystallographic and biochemical studies have revealed a role for NADP\n                    <jats:sup>+<\/jats:sup>\n                    s in maintaining the catalytic activity by stabilizing the multimeric G6PD conformation, other potential roles for NADP\n                    <jats:sup>+<\/jats:sup>\n                    s have not been evaluated. Here, we determined the high resolution cryo-electron microscopy structures of human wild-type G6PD in the absence of bound ligands and a catalytic G6PD-D200N mutant bound to NADP\n                    <jats:sup>+<\/jats:sup>\n                    c and NADP\n                    <jats:sup>+<\/jats:sup>\n                    s in the absence or presence of G6P. A comparison of these structures, together with previously reported structures, reveals that the unliganded human G6PD forms a mixture of dimers and tetramers with similar overall folds, and binding of NADP\n                    <jats:sup>+<\/jats:sup>\n                    s induces a structural ordering of a C-terminal extension region and allosterically regulates G6P binding and catalysis. These studies have implications for understanding G6PD deficiencies and for therapy of G6PD-mediated disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2119695119","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T14:35:24Z","timestamp":1657636524000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Allosteric role of a structural NADP\n                    <sup>+<\/sup>\n                    molecule in glucose-6-phosphate dehydrogenase activity"],"prefix":"10.1073","volume":"119","author":[{"given":"Xuepeng","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, 19104"},{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7996-0279","authenticated-orcid":false,"given":"Kathryn","family":"Kixmoeller","sequence":"additional","affiliation":[{"name":"Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elana","family":"Baltrusaitis","sequence":"additional","affiliation":[{"name":"Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6755-7725","authenticated-orcid":false,"given":"Xiaolu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4373-4752","authenticated-orcid":false,"given":"Ronen","family":"Marmorstein","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA, 19104"},{"name":"Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, 19104"},{"name":"Graduate Group in Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA, 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"e_1_3_5_1_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi972069y"},{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1017"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2014.913788"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/jam.13509"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830420111"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2015.11.006"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60073-2"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107788"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050253"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/1871529X11313010008"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.638885"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.06.005"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12140"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00104-0"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905002350"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2022790118"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(71)90406-1"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(70)90769-2"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12638"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.035352.108"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122069"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2012.01.001"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.10.002"},{"key":"e_1_3_5_24_2","first-page":"601","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"67","author":"Anonymous; WHO Working Group","year":"1989","unstructured":"Anonymous; WHO Working Group, Glucose-6-phosphate dehydrogenase deficiency. 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