{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:24:36Z","timestamp":1787646276468,"version":"build-2736575974"},"reference-count":53,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35 GM152206"],"award-info":[{"award-number":["R35 GM152206"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10OD030470-01"],"award-info":[{"award-number":["S10OD030470-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1-P30-GM124166"],"award-info":[{"award-number":["1-P30-GM124166"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jbc.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.jbc.2026.113091","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T23:30:50Z","timestamp":1777332650000},"page":"113091","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure and enzymology of glutaminase S482C and H461L variants associated with excess brain glutamate and neurological disease"],"prefix":"10.1016","volume":"302","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0035-709X","authenticated-orcid":false,"given":"Cl\u00e9a S.","family":"Crane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thora K.","family":"McIssac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn K.","family":"Milano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-5897","authenticated-orcid":false,"given":"Richard A.","family":"Cerione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7117-3684","authenticated-orcid":false,"given":"Scott M.","family":"Ulrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jbc.2026.113091_bib1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev.nu.15.070195.001025","article-title":"Regulation of glutaminase activity and glutamine metabolism","volume":"15","author":"Curthoys","year":"1995","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.jbc.2026.113091_bib2","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4155\/fmc-2016-0190","article-title":"A tale of two glutaminases: homologous enzymes with distinct roles in tumorigenesis","volume":"9","author":"Katt","year":"2017","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.jbc.2026.113091_bib3","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/j.1471-4159.2006.03913.x","article-title":"The glutamate\/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer","volume":"98","author":"Bak","year":"2006","journal-title":"J. Neurochem."},{"key":"10.1016\/j.jbc.2026.113091_bib4","series-title":"Glutamate and ATP at the Interface of Metabolism and Signaling in the Brain","author":"Parpura","year":"2014"},{"key":"10.1016\/j.jbc.2026.113091_bib5","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/jnc.15811","article-title":"Milestone review: metabolic dynamics of glutamate and GABA mediated neurotransmission - the essential roles of astrocytes","volume":"166","author":"Andersen","year":"2023","journal-title":"J. Neurochem."},{"key":"10.1016\/j.jbc.2026.113091_bib6","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/acn3.522","article-title":"GLS loss of function causes autosomal recessive spastic ataxia and optic atrophy","volume":"5","author":"Lynch","year":"2018","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"10.1016\/j.jbc.2026.113091_bib7","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1001\/jamaneurol.2018.2941","article-title":"Identification of a loss-of-function mutation in the context of glutaminase deficiency and neonatal epileptic encephalopathy","volume":"76","author":"Rumping","year":"2019","journal-title":"JAMA Neurol."},{"key":"10.1016\/j.jbc.2026.113091_bib8","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.tins.2021.01.001","article-title":"Excitotoxicity revisited: mitochondria on the verge of a nervous breakdown","volume":"44","author":"Plotegher","year":"2021","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.jbc.2026.113091_bib9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40035-021-00278-7","article-title":"Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration","volume":"11","author":"Verma","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"10.1016\/j.jbc.2026.113091_bib10","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.3233\/JAD-160763","article-title":"Role of glutamate and NMDA receptors in alzheimer\u2019s disease","volume":"57","author":"Wang","year":"2017","journal-title":"J. Alzheimers Dis. JAD"},{"key":"10.1016\/j.jbc.2026.113091_bib11","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.3390\/ijms25115587","article-title":"Revisiting glutamate excitotoxicity in amyotrophic lateral sclerosis and age-related neurodegeneration","volume":"25","author":"Arnold","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jbc.2026.113091_bib12","doi-asserted-by":"crossref","first-page":"15195","DOI":"10.1523\/JNEUROSCI.2051-11.2011","article-title":"Glutaminase dysregulation in HIV-1-Infected human microglia mediates neurotoxicity: relevant to HIV-1-Associated neurocognitive disorders","volume":"31","author":"Huang","year":"2011","journal-title":"J. Neurosci."},{"key":"10.1016\/j.jbc.2026.113091_bib13","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41582-022-00651-8","article-title":"The metabolic basis of epilepsy","volume":"18","author":"Rho","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.jbc.2026.113091_bib14","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbi.2017.06.007","article-title":"Glutaminase C overexpression in the brain induces learning deficits, synaptic dysfunctions, and neuroinflammation in mice","volume":"66","author":"Wang","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.jbc.2026.113091_bib15","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/hmg\/ddy330","article-title":"GLS hyperactivity causes glutamate excess, infantile cataract and profound developmental delay","volume":"28","author":"Rumping","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.jbc.2026.113091_bib16","first-page":"217","article-title":"A second case of glutaminase hyperactivity: expanding the phenotype with epilepsy","volume":"64","author":"Rumping","year":"2023","journal-title":"JIMD Rep."},{"key":"10.1016\/j.jbc.2026.113091_bib17","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/jimd.12180","article-title":"Inborn errors of enzymes in glutamate metabolism","volume":"43","author":"Rumping","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.jbc.2026.113091_bib18","doi-asserted-by":"crossref","first-page":"7705","DOI":"10.1073\/pnas.1116573109","article-title":"Structural basis for the allosteric inhibitory mechanism of human kidney-type glutaminase (KGA) and its regulation by raf-mek-erk signaling in cancer cell metabolism","volume":"109","author":"Thangavelu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2026.113091_bib19","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1111\/j.1471-4159.1971.tb05078.x","article-title":"Activation of pig brain glutaminase","volume":"18","author":"Svenneby","year":"1971","journal-title":"J. Neurochem."},{"key":"10.1016\/j.jbc.2026.113091_bib20","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0021-9258(18)56979-9","article-title":"Phosphate-activated glutaminase in kidney and other tissues","volume":"178","author":"Errera","year":"1949","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113091_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2022.101564","article-title":"High-resolution structures of mitochondrial glutaminase C tetramers indicate conformational changes upon phosphate binding","volume":"298","author":"Nguyen","year":"2022","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113091_bib22","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/S0021-9258(19)77352-9","article-title":"Preparation and some properties of a phosphateactivated glutaminase from kidneys","volume":"233","author":"Sayre","year":"1958","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113091_bib23","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1073\/pnas.1112495109","article-title":"Mitochondrial localization and structure-based phosphate activation mechanism of glutaminase C with implications for cancer metabolism","volume":"109","author":"Cassago","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jbc.2026.113091_bib24","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1432-1033.1978.tb12182.x","article-title":"Intramitochondrial and extramitochondrial concentrations of adenine nucleotides and inorganic phosphate in isolated hepatocytes from fasted rats","volume":"84","author":"Akerboom","year":"1978","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.jbc.2026.113091_bib25","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1023\/A:1007668801570","article-title":"Phosphate-activated glutaminase and mitochondrial glutamine transport in the brain","volume":"25","author":"Kvamme","year":"2000","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.jbc.2026.113091_bib26","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1042\/bj2070561","article-title":"Inhibition by glutamate of phosphate-dependent glutaminase of rat kidney","volume":"207","author":"Shapiro","year":"1982","journal-title":"Biochem. J."},{"key":"10.1016\/j.jbc.2026.113091_bib27","doi-asserted-by":"crossref","first-page":"867S","DOI":"10.3945\/ajcn.2009.27462BB","article-title":"The blood-brain barrier and glutamate","volume":"90","author":"Hawkins","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.jbc.2026.113091_bib28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0074-7742(08)60289-5","article-title":"Transport and metabolism of glutamate and GABA in neurons are glial cells","volume":"22","author":"Schousboe","year":"1981","journal-title":"Int. Rev. Neurobiol."},{"key":"10.1016\/j.jbc.2026.113091_bib29","doi-asserted-by":"crossref","first-page":"1026S","DOI":"10.1093\/jn\/130.4.1026S","article-title":"Compartmentation of brain glutamate metabolism in neurons and glia","volume":"130","author":"Daikhin","year":"2000","journal-title":"J. Nutr."},{"key":"10.1016\/j.jbc.2026.113091_bib30","doi-asserted-by":"crossref","first-page":"10764","DOI":"10.1021\/bi201613d","article-title":"Full-length human glutaminase in complex with an allosteric inhibitor","volume":"50","author":"DeLaBarre","year":"2011","journal-title":"Biochemistry"},{"key":"10.1016\/j.jbc.2026.113091_bib31","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.biochi.2021.03.009","article-title":"Structure and activation mechanism of the human liver-type glutaminase GLS2","volume":"185","author":"Ferreira","year":"2021","journal-title":"Biochimie"},{"key":"10.1016\/j.jbc.2026.113091_bib32","doi-asserted-by":"crossref","first-page":"FDD79","DOI":"10.4155\/fdd-2022-0011","article-title":"Alone and together: current approaches to targeting glutaminase enzymes as part of anti-cancer therapies","volume":"4","author":"Nguyen","year":"2022","journal-title":"Future Drug Discov."},{"key":"10.1016\/j.jbc.2026.113091_bib33","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s12551-019-00602-6","article-title":"Structures, functions, and mechanisms of filament forming enzymes: a renaissance of enzyme filamentation","volume":"11","author":"Park","year":"2019","journal-title":"Biophys. Rev."},{"key":"10.1016\/j.jbc.2026.113091_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.sbi.2023.102530","article-title":"Greater than the sum of parts: mechanisms of metabolic regulation by enzyme filaments","volume":"79","author":"Hvorecny","year":"2023","journal-title":"Curr. Opin. Struct. Biol."},{"key":"10.1016\/j.jbc.2026.113091_bib35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ceb.2020.04.006","article-title":"Filament formation by metabolic enzymes\u2014A new twist on regulation","volume":"66","author":"Lynch","year":"2020","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.jbc.2026.113091_bib36","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1016\/j.molcel.2022.03.016","article-title":"Filamentous GLS1 promotes ROS-induced apoptosis upon glutamine deprivation via insufficient asparagine synthesis","volume":"82","author":"Jiang","year":"2022","journal-title":"Mol. Cell"},{"key":"10.1016\/j.jbc.2026.113091_bib37","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1038\/s41594-023-01118-0","article-title":"Molecular mechanism of glutaminase activation through filamentation and the role of filaments in mitophagy protection","volume":"30","author":"Adamoski","year":"2023","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.jbc.2026.113091_bib38","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1038\/s41467-024-46351-3","article-title":"Filament formation drives catalysis by glutaminase enzymes important in cancer progression","volume":"15","author":"Feng","year":"2024","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jbc.2026.113091_bib39","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41422-023-00886-0","article-title":"Structural basis for activation and filamentation of glutaminase","volume":"34","author":"Guo","year":"2023","journal-title":"Cell Res."},{"key":"10.1016\/j.jbc.2026.113091_bib40","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.73368","article-title":"Cryo-EM structures of CTP synthase filaments reveal mechanism of pH-sensitive assembly during budding yeast starvation","volume":"10","author":"Hansen","year":"2021","journal-title":"Elife"},{"key":"10.1016\/j.jbc.2026.113091_bib41","doi-asserted-by":"crossref","first-page":"28009","DOI":"10.1074\/jbc.M113.501346","article-title":"Active glutaminase C self-assembles into a supratetrameric oligomer that can be disrupted by an allosteric inhibitor","volume":"288","author":"Ferreira","year":"2013","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jbc.2026.113091_bib42","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.1600200","article-title":"Fundamentals of cancer metabolism","volume":"2","author":"DeBerardinis","year":"2016","journal-title":"Sci. Adv."},{"key":"10.1016\/j.jbc.2026.113091_bib43","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.1172\/JCI69600","article-title":"Glutamine and cancer: cell biology, physiology, and clinical opportunities","volume":"123","author":"Hensley","year":"2013","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.jbc.2026.113091_bib44","doi-asserted-by":"crossref","first-page":"861","DOI":"10.3109\/14756366.2011.622272","article-title":"BPTES inhibition of hGA(124-551), a truncated form of human kidney-type glutaminase","volume":"27","author":"Hartwick","year":"2012","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"10.1016\/j.jbc.2026.113091_bib45","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.neuint.2014.12.003","article-title":"Effect of lysine to alanine mutations on the phosphate activation and BPTES inhibition of glutaminase","volume":"88","author":"McDonald","year":"2015","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.jbc.2026.113091_bib46","doi-asserted-by":"crossref","first-page":"5724","DOI":"10.1021\/bi800097h","article-title":"Functional and structural characterization of four glutaminases from Escherichia coli and Bacillus subtilis","volume":"47","author":"Brown","year":"2008","journal-title":"Biochemistry"},{"key":"10.1016\/j.jbc.2026.113091_bib47","doi-asserted-by":"crossref","first-page":"3337","DOI":"10.1242\/jcs.03061","article-title":"Brain-specific BNIP-2-homology protein Caytaxin relocalises glutaminase to neurite terminals and reduces glutamate levels","volume":"119","author":"Buschdorf","year":"2006","journal-title":"J. Cell Sci."},{"key":"10.1016\/j.jbc.2026.113091_bib48","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.biochi.2012.11.016","article-title":"Bmcc1s interacts with the phosphate-activated glutaminase in the brain","volume":"95","author":"Boulay","year":"2013","journal-title":"Biochimie"},{"key":"10.1016\/j.jbc.2026.113091_bib49","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","article-title":"Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix","volume":"75","author":"Liebschner","year":"2019","journal-title":"Acta Crystallogr. Sect. Struct. Biol."},{"key":"10.1016\/j.jbc.2026.113091_bib50","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1107\/S0907444904019158","article-title":"Coot: model-building tools for molecular graphics","volume":"60","author":"Emsley","year":"2004","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.jbc.2026.113091_bib51","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","article-title":"Processing of X-ray diffraction data collected in oscillation mode","volume":"276","author":"Otwinowski","year":"1997","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.jbc.2026.113091_bib52","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.jbc.2026.113091_bib53","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1042\/bj1050691","article-title":"The equilibrium constants of the glutamate dehydrogenase systems","volume":"105","author":"Engel","year":"1967","journal-title":"Biochem J"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925826019630?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925826019630?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:38:32Z","timestamp":1787643512000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925826019630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["S0021925826019630"],"URL":"https:\/\/doi.org\/10.1016\/j.jbc.2026.113091","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structure and enzymology of glutaminase S482C and H461L variants associated with excess brain glutamate and neurological disease","name":"articletitle","label":"Article Title"},{"value":"Journal of Biological Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jbc.2026.113091","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.","name":"copyright","label":"Copyright"}],"article-number":"113091"}}