{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:30:09Z","timestamp":1789450209533,"version":"build-2803163510"},"reference-count":61,"publisher":"National Academy of Sciences","issue":"4","license":[{"start":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T00:00:00Z","timestamp":1611014400000},"content-version":"vor","delay-in-days":1,"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":["HD084422"],"award-info":[{"award-number":["HD084422"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19K23713"],"award-info":[{"award-number":["JP19K23713"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K15741"],"award-info":[{"award-number":["JP20K15741"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Max-Planck Society","award":["1160193"],"award-info":[{"award-number":["1160193"]}]},{"DOI":"10.13039\/501100007769","name":"Max-Planck-Institut f\u00fcr Terrestrische Mikrobiologie","doi-asserted-by":"publisher","award":["MPG 190003"],"award-info":[{"award-number":["MPG 190003"]}],"id":[{"id":"10.13039\/501100007769","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":[[2021,1,26]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Mechanism of the loss of activity of the most severe patient-derived mutants of glucose-6-phosphate dehydrogenase (G6PD) deficiency has remained elusive despite the availability of the G6PD structures for decades. Structural and biophysical investigations have revealed a common mechanism and dynamics of how these mutations hinder the substrate-binding site, reducing enzymatic activity. These are triggered by a long-distance propagation of structural defects at the dimer interface and the binding site of the noncatalytic cofactor. These structural distortions are found among all of the class I mutants investigated, providing critical clues for drug design to address G6PD deficiency by correcting the structural defects.<\/jats:p>","DOI":"10.1073\/pnas.2022790118","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T17:10:11Z","timestamp":1611076211000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":35,"title":["Long-range structural defects by pathogenic mutations in most severe glucose-6-phosphate dehydrogenase deficiency"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1842-6934","authenticated-orcid":false,"given":"Naoki","family":"Horikoshi","sequence":"first","affiliation":[{"name":"Life Science Center for Survival Dynamics, University of Tsukuba, Ibaraki 305-8577, Japan;"},{"name":"Biological Sciences Division, SLAC National Accelerator Laboratory, Menlo Park, CA 94025;"},{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhee","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Gati","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, SLAC National Accelerator Laboratory, Menlo Park, CA 94025;"},{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Matsui","sequence":"additional","affiliation":[{"name":"Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2703-1678","authenticated-orcid":false,"given":"Carlos","family":"Castillo-Orellana","sequence":"additional","affiliation":[{"name":"Departamento de F\u00edsico-Qu\u00edmica, Facultad de Ciencias Qu\u00edmicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 94030000, Chile;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Raub","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana A.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Jabbarpour","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, SLAC National Accelerator Laboratory, Menlo Park, CA 94025;"},{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9393-2880","authenticated-orcid":false,"given":"Alexander","family":"Batyuk","sequence":"additional","affiliation":[{"name":"Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, CA 94025"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Broweleit","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8358-2960","authenticated-orcid":false,"given":"Xinyu","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-3046","authenticated-orcid":false,"given":"Andrew","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Broweleit","sequence":"additional","affiliation":[{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"V\u00f6hringer-Martinez","sequence":"additional","affiliation":[{"name":"Departamento de F\u00edsico-Qu\u00edmica, Facultad de Ciencias Qu\u00edmicas, Universidad de Concepci\u00f3n, Concepci\u00f3n 94030000, Chile;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6691-8733","authenticated-orcid":false,"given":"Daria","family":"Mochly-Rosen","sequence":"additional","affiliation":[{"name":"Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5896-7968","authenticated-orcid":false,"given":"Soichi","family":"Wakatsuki","sequence":"additional","affiliation":[{"name":"Biological Sciences Division, SLAC National Accelerator Laboratory, Menlo Park, CA 94025;"},{"name":"Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2012.01.001"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.208"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2015.11.006"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2016.01.010"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2008.12.005"},{"key":"e_1_3_4_6_2","volume-title":"Biochemistry","author":"Berg J. M.","year":"2002","unstructured":"J. M. Berg, J. L. Tymoczko, L. Stryer, Biochemistry (W. H. Freeman and Co, New York, ed. 5, 2002).","edition":"5"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/acprof:oso\/9780198717478.001.0001"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-077412"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60073-2"},{"key":"e_1_3_4_10_2","first-page":"601","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"67","author":"WHO Working Group","year":"1989","unstructured":"WHO Working Group, Glucose-6-phosphate dehydrogenase deficiency. Bull. World Health Organ. 67, 601\u2013611 (1989).","journal-title":"Bull. World Health Organ."},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0268-960X(96)90019-3"},{"key":"e_1_3_4_12_2","first-page":"1303","article-title":"Glucose 6-phosphate dehydrogenase deficiency: From genotype to phenotype","volume":"91","author":"Luzzatto L.","year":"2006","unstructured":"L. Luzzatto, Glucose 6-phosphate dehydrogenase deficiency: From genotype to phenotype. Haematologica 91, 1303\u20131306 (2006).","journal-title":"Haematologica"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122069"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00104-0"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444905002350"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(71)80091-8"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(72)90101-5"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1973.tb02746.x"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.035352.108"},{"key":"e_1_3_4_20_2","article-title":"Structural analysis of clinically relevant pathogenic G6PD variants reveals the importance of tetramerization for G6PD activity","volume":"2017","author":"Cunningham A. D.","year":"2017","unstructured":"A. D. Cunningham, D. Mochly-Rosen, Structural analysis of clinically relevant pathogenic G6PD variants reveals the importance of tetramerization for G6PD activity. Matters (Zur.) 2017, (2017).","journal-title":"Matters (Zur.)"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06447-z"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201900341"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.05.003"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms151121179"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms161226124"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.048"},{"key":"e_1_3_4_27_2","first-page":"446","article-title":"A novel de novo mutation in the G6PD gene in a Korean boy with glucose-6-phosphate dehydrogenase deficiency: Case report","volume":"45","author":"Jang M.-A.","year":"2015","unstructured":"M.-A. Jang ., A novel de novo mutation in the G6PD gene in a Korean boy with glucose-6-phosphate dehydrogenase deficiency: Case report. Ann. Clin. Lab. Sci. 45, 446\u2013448 (2015).","journal-title":"Ann. Clin. Lab. Sci."},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00211027"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583507004635"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889812007662"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.1995.0010"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004310000652"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.1.257.bloodjournal851257"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)64298-3"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1992.tb06409.x"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.18388\/abp.2007_3192"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-9525(92)90080-N"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(88)90263-8"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50504-X"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)77379-7"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00895a006"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)81885-7"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)41732-8"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1978.tb00858.x"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910045749"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2015.07.003"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909052925"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909042073"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1911489116"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b02100"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807002853"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889892001663"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889895007047"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4193"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2016.04.012"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3235"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4067"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2022790118","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2022790118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T06:43:15Z","timestamp":1649832195000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2022790118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,18]]},"references-count":61,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,1,26]]}},"alternative-id":["10.1073\/pnas.2022790118"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2022790118","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,18]]},"assertion":[{"value":"2021-01-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2022790118"}}