{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:59:44Z","timestamp":1790909984256,"version":"4.1.0"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:00:00Z","timestamp":1663718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-05426"],"award-info":[{"award-number":["RGPIN-05426"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-03929"],"award-info":[{"award-number":["RGPIN-03929"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011889","name":"Diamond Light Source","doi-asserted-by":"publisher","award":["mx18598"],"award-info":[{"award-number":["mx18598"]}],"id":[{"id":"10.13039\/100011889","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011889","name":"Diamond Light Source","doi-asserted-by":"publisher","award":["mx24948"],"award-info":[{"award-number":["mx24948"]}],"id":[{"id":"10.13039\/100011889","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"crossref","award":["Ken Murray Research Professorship"],"award-info":[{"award-number":["Ken Murray Research Professorship"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","award":["RP\\EA\\180016"],"award-info":[{"award-number":["RP\\EA\\180016"]}],"id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","award":["Tier I CRC"],"award-info":[{"award-number":["Tier I CRC"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosbiology.org"],"crossmark-restriction":false},"short-container-title":["PLoS Biol"],"abstract":"<jats:p>Primary familial brain calcification (PFBC) is characterised by abnormal deposits of calcium phosphate within various regions of the brain that are associated with severe cognitive impairments, psychiatric conditions, and movement disorders. Recent studies in diverse populations have shown a link between mutations in myogenesis-regulating glycosidase (MYORG) and the development of this disease. MYORG is a member of glycoside hydrolase (GH) family 31 (GH31) and, like the other mammalian GH31 enzyme \u03b1-glucosidase II, this enzyme is found in the lumen of the endoplasmic reticulum (ER). Though presumed to act as an \u03b1-glucosidase due to its localization and sequence relatedness to \u03b1-glucosidase II, MYORG has never been shown to exhibit catalytic activity. Here, we show that MYORG is an \u03b1-galactosidase and present the high-resolution crystal structure of MYORG in complex with substrate and inhibitor. Using these structures, we map detrimental mutations that are associated with MYORG-associated brain calcification and define how these mutations may drive disease progression through loss of enzymatic activity. Finally, we also detail the thermal stabilisation of MYORG afforded by a clinically approved small molecule ligand, opening the possibility of using pharmacological chaperones to enhance the activity of mutant forms of MYORG.<\/jats:p>","DOI":"10.1371\/journal.pbio.3001764","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T17:29:13Z","timestamp":1663781353000},"page":"e3001764","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":23,"title":["The primary familial brain calcification-associated protein MYORG is an \u03b1-galactosidase with restricted substrate specificity"],"prefix":"10.1371","volume":"20","author":[{"given":"Richard W.","family":"Meek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Brockerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osei B.","family":"Fordwour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley F.","family":"Zandberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon J.","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6897-5558","authenticated-orcid":true,"given":"David J.","family":"Vocadlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"issue":"Pt 11","key":"pbio.3001764.ref001","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1093\/brain\/awt255","article-title":"Phenotypic spectrum of probable and genetically-confirmed idiopathic basal ganglia calcification","volume":"136","author":"G Nicolas","year":"2013","journal-title":"Brain"},{"issue":"9","key":"pbio.3001764.ref002","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1038\/ng.2723","article-title":"Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice","volume":"45","author":"A Keller","year":"2013","journal-title":"Nat Genet"},{"issue":"6","key":"pbio.3001764.ref003","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/ng.3289","article-title":"Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export","volume":"47","author":"A Legati","year":"2015","journal-title":"Nat Genet"},{"issue":"2","key":"pbio.3001764.ref004","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1212\/WNL.0b013e31827ccf34","article-title":"Mutation of the PDGFRB gene as a cause of idiopathic basal ganglia calcification","volume":"80","author":"G Nicolas","year":"2013","journal-title":"Neurology"},{"issue":"3","key":"pbio.3001764.ref005","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/ng.1077","article-title":"Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis","volume":"44","author":"C Wang","year":"2012","journal-title":"Nat Genet"},{"issue":"6","key":"pbio.3001764.ref006","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.neuron.2018.05.037","article-title":"Biallelic Mutations in MYORG Cause Autosomal Recessive Primary Familial Brain Calcification","volume":"98","author":"XP Yao","year":"2018","journal-title":"Neuron"},{"issue":"3","key":"pbio.3001764.ref007","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.ajhg.2020.02.007","article-title":"Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification","volume":"106","author":"LV Schottlaender","year":"2020","journal-title":"Am J Hum Genet"},{"issue":"28","key":"pbio.3001764.ref008","doi-asserted-by":"crossref","first-page":"9366","DOI":"10.1074\/jbc.RA119.011376","article-title":"Interplay between primary familial brain calcification-associated SLC20A2 and XPR1 phosphate transporters requires inositol polyphosphates for control of cellular phosphate homeostasis","volume":"295","author":"U L\u00f3pez-S\u00e1nchez","year":"2020","journal-title":"J Biol Chem"},{"issue":"11","key":"pbio.3001764.ref009","doi-asserted-by":"crossref","first-page":"e0143407","DOI":"10.1371\/journal.pone.0143407","article-title":"Functional Characterization of Germline Mutations in PDGFB and PDGFRB in Primary Familial Brain Calcification","volume":"10","author":"M Vanlandewijck","year":"2015","journal-title":"PLoS ONE"},{"issue":"4","key":"pbio.3001764.ref010","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1074\/jbc.M005458200","article-title":"JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells","volume":"276","author":"M Aurrand-Lions","year":"2001","journal-title":"J Biol Chem"},{"issue":"43","key":"pbio.3001764.ref011","doi-asserted-by":"crossref","first-page":"29666","DOI":"10.1074\/jbc.M109.034041","article-title":"NET37, a nuclear envelope transmembrane protein with glycosidase homology, is involved in myoblast differentiation","volume":"284","author":"K Datta","year":"2009","journal-title":"J Biol Chem"},{"issue":"Database issue","key":"pbio.3001764.ref012","doi-asserted-by":"crossref","first-page":"D490","DOI":"10.1093\/nar\/gkt1178","article-title":"The carbohydrate-active enzymes database (CAZy) in 2013","volume":"42","author":"V Lombard","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"5","key":"pbio.3001764.ref013","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S0959-440X(97)80072-3","article-title":"Structural and sequence-based classification of glycoside hydrolases","volume":"7","author":"B Henrissat","year":"1997","journal-title":"Curr Opin Struct Biol"},{"issue":"5638","key":"pbio.3001764.ref014","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1126\/science.1088176","article-title":"Nuclear membrane proteins with potential disease links found by subtractive proteomics","volume":"301","author":"EC Schirmer","year":"2003","journal-title":"Science"},{"issue":"3","key":"pbio.3001764.ref015","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1073\/pnas.91.3.913","article-title":"Role of N-linked oligosaccharide recognition, glucose trimming, and calnexin in glycoprotein folding and quality control","volume":"91","author":"C Hammond","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"pbio.3001764.ref016","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1091\/mbc.6.9.1173","article-title":"Transient, lectin-like association of calreticulin with folding intermediates of cellular and viral glycoproteins","volume":"6","author":"JR Peterson","year":"1995","journal-title":"Mol Biol Cell"},{"issue":"1","key":"pbio.3001764.ref017","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1023\/A:1005925819741","article-title":"Plant alpha-glucosidases of the glycoside hydrolase family 31. Molecular properties, substrate specificity, reaction mechanism, and comparison with family members of different origin","volume":"37","author":"TP Frandsen","year":"1998","journal-title":"Plant Mol Biol"},{"issue":"32","key":"pbio.3001764.ref018","doi-asserted-by":"crossref","first-page":"E4630","DOI":"10.1073\/pnas.1604463113","article-title":"Structures of mammalian ER \u03b1-glucosidase II capture the binding modes of broad-spectrum iminosugar antivirals","volume":"113","author":"AT Caputo","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"pbio.3001764.ref019","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.cmet.2008.02.012","article-title":"Opposing effects of dietary protein and sugar regulate a transcriptional target of Drosophila insulin-like peptide signaling","volume":"7","author":"S Buch","year":"2008","journal-title":"Cell Metab"},{"issue":"8","key":"pbio.3001764.ref020","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1046\/j.1432-1327.2001.02104.x","article-title":"Carboxyl group of residue Asp647 as possible proton donor in catalytic reaction of alpha-glucosidase from Schizosaccharomyces pombe","volume":"268","author":"M Okuyama","year":"2001","journal-title":"Eur J Biochem"},{"issue":"3","key":"pbio.3001764.ref021","doi-asserted-by":"crossref","first-page":"e0004524","DOI":"10.1371\/journal.pntd.0004524","article-title":"Iminosugars Inhibit Dengue Virus Production via Inhibition of ER Alpha-Glucosidases\u2014Not Glycolipid Processing Enzymes","volume":"10","author":"AC Sayce","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"issue":"5","key":"pbio.3001764.ref022","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s40265-019-01090-4","article-title":"Migalastat: A Review in Fabry Disease","volume":"79","author":"EH McCafferty","year":"2019","journal-title":"Drugs"},{"issue":"12","key":"pbio.3001764.ref023","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.chembiol.2011.10.012","article-title":"The molecular basis of pharmacological chaperoning in human \u03b1-galactosidase","volume":"18","author":"AI Guce","year":"2011","journal-title":"Chem Biol"},{"issue":"1","key":"pbio.3001764.ref024","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1042\/BJ20150261","article-title":"Structural and biochemical characterization of novel bacterial \u03b1-galactosidases belonging to glycoside hydrolase family 31","volume":"469","author":"T Miyazaki","year":"2015","journal-title":"Biochem J"},{"issue":"24","key":"pbio.3001764.ref025","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.1021\/jp403355e","article-title":"Determination of proton affinities and acidity constants of sugars","volume":"117","author":"S Feng","year":"2013","journal-title":"J Phys Chem A"},{"issue":"7","key":"pbio.3001764.ref026","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1021\/ja057904a","article-title":"Expanding the thioglycoligase strategy to the synthesis of alpha-linked thioglycosides allows structural investigation of the parent enzyme\/substrate complex","volume":"128","author":"YW Kim","year":"2006","journal-title":"J Am Chem Soc"},{"issue":"W1","key":"pbio.3001764.ref027","doi-asserted-by":"crossref","first-page":"W402","DOI":"10.1093\/nar\/gkz297","article-title":"The PSIPRED Protein Analysis Workbench: 20 years on","volume":"47","author":"DWA Buchan","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"pbio.3001764.ref028","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1093\/bioinformatics\/btu744","article-title":"DISOPRED3: precise disordered region predictions with annotated protein-binding activity","volume":"31","author":"DT Jones","year":"2015","journal-title":"Bioinformatics"},{"key":"pbio.3001764.ref029","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1186\/1471-2105-10-159","article-title":"Transmembrane protein topology prediction using support vector machines","volume":"10","author":"T Nugent","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"pbio.3001764.ref030","doi-asserted-by":"crossref","first-page":"20575","DOI":"10.1038\/srep20575","article-title":"Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control","volume":"6","author":"T Satoh","year":"2016","journal-title":"Sci Rep"},{"issue":"14","key":"pbio.3001764.ref031","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1002\/1873-3468.13804","article-title":"Crystal structure of the Enterococcus faecalis \u03b1-N-acetylgalactosaminidase, a member of the glycoside hydrolase family 31","volume":"594","author":"T Miyazaki","year":"2020","journal-title":"FEBS Lett"},{"issue":"2","key":"pbio.3001764.ref032","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"O Trott","year":"2010","journal-title":"J Comput Chem"},{"issue":"1","key":"pbio.3001764.ref033","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s41572-018-0025-4","article-title":"Lysosomal storage diseases","volume":"4","author":"FM Platt","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"1\u20132","key":"pbio.3001764.ref034","first-page":"1","article-title":"Lysosomal storage diseases","volume":"2","author":"CR Ferreira","year":"2017","journal-title":"Transl Sci Rare Dis"},{"issue":"1","key":"pbio.3001764.ref035","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/4801","article-title":"Accelerated transport and maturation of lysosomal alpha-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor","volume":"5","author":"JQ Fan","year":"1999","journal-title":"Nat Med"},{"issue":"29","key":"pbio.3001764.ref036","doi-asserted-by":"crossref","first-page":"18443","DOI":"10.1074\/jbc.273.29.18443","article-title":"Post-translational processing of the insulin-like growth factor-2 precursor. Analysis of O-glycosylation and endoproteolysis","volume":"273","author":"SJ Duguay","year":"1998","journal-title":"J Biol Chem"},{"issue":"8","key":"pbio.3001764.ref037","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/(SICI)1096-9888(199608)31:8<893::AID-JMS374>3.0.CO;2-S","article-title":"Characterization of O-glycosylated precursors of insulin-like growth factor II by matrix-assisted laser desorption\/ionization mass spectrometry","volume":"31","author":"S Jespersen","year":"1996","journal-title":"J Mass Spectrom"},{"issue":"7","key":"pbio.3001764.ref038","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.braindev.2021.04.002","article-title":"First pediatric case with primary familial brain calcification due to a novel variant on the MYORG gene and review of the literature","volume":"43","author":"L Tekin Orgun","year":"2021","journal-title":"Brain Dev"},{"issue":"2","key":"pbio.3001764.ref039","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1093\/brain\/awy343","article-title":"A biallelic mutation links MYORG to autosomal-recessive primary familial brain calcification","volume":"142","author":"Y Forouhideh","year":"2019","journal-title":"Brain"},{"issue":"7","key":"pbio.3001764.ref040","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1038\/mt.2015.62","article-title":"Pharmacological Chaperone Therapy: Preclinical Development, Clinical Translation, and Prospects for the Treatment of Lysosomal Storage Disorders","volume":"23","author":"G Parenti","year":"2015","journal-title":"Mol Ther"},{"issue":"2","key":"pbio.3001764.ref041","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0167-4838(96)00136-7","article-title":"Site-directed mutagenesis of the N-linked glycosylation site in platelet-derived growth factor B-chain results in diminished intracellular retention","volume":"1298","author":"DM Kaetzel","year":"1996","journal-title":"Biochim Biophys Acta"},{"issue":"5","key":"pbio.3001764.ref042","doi-asserted-by":"crossref","first-page":"279","DOI":"10.4161\/bioe.22966","article-title":"Gene gymnastics: Synthetic biology for baculovirus expression vector system engineering","volume":"4","author":"LS Vijayachandran","year":"2013","journal-title":"Bioengineered"},{"issue":"3","key":"pbio.3001764.ref043","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nmeth1010","article-title":"Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC","volume":"4","author":"MZ Li","year":"2007","journal-title":"Nat Methods"},{"key":"pbio.3001764.ref044","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-1-62703-691-7_7","article-title":"OmniBac: universal multigene transfer plasmids for baculovirus expression vector systems","volume":"1091","author":"DB Thimiri Govinda Raj","year":"2014","journal-title":"Methods Mol Biol"},{"issue":"1","key":"pbio.3001764.ref045","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jsb.2010.02.010","article-title":"New baculovirus expression tools for recombinant protein complex production","volume":"172","author":"S Trowitzsch","year":"2010","journal-title":"J Struct Biol"},{"issue":"2","key":"pbio.3001764.ref046","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.tibs.2011.10.005","article-title":"MultiBac: expanding the research toolbox for multiprotein complexes","volume":"37","author":"C Bieniossek","year":"2012","journal-title":"Trends Biochem Sci"},{"issue":"32","key":"pbio.3001764.ref047","doi-asserted-by":"crossref","first-page":"8574","DOI":"10.1021\/acs.jafc.8b01041","article-title":"Capillary Electrophoresis Analysis of Bovine Milk Oligosaccharides Permits an Assessment of the Influence of Diet and the Discovery of Nine Abundant Sulfated Analogues","volume":"66","author":"SD Vicaretti","year":"2018","journal-title":"J Agric Food Chem"},{"issue":"Pt 2","key":"pbio.3001764.ref048","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1107\/S2059798317017235","article-title":"DIALS: implementation and evaluation of a new integration package","volume":"74","author":"G Winter","year":"2018","journal-title":"Acta Crystallogr D Struct Biol"},{"issue":"7","key":"pbio.3001764.ref049","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1107\/S0907444913000061","article-title":"How good are my data and what is the resolution?","volume":"69","author":"PR Evans","year":"2013","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 11","key":"pbio.3001764.ref050","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1107\/S0907444913022750","article-title":"Phaser.MRage: automated molecular replacement","volume":"69","author":"G Bunk\u00f3czi","year":"2013","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"3","key":"pbio.3001764.ref051","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1107\/S0021889808006985","article-title":"CHAINSAW: a program for mutating pdb files used as templates in molecular replacement","volume":"41","author":"N. Stein","year":"2008","journal-title":"J Appl Cryst"},{"issue":"Pt 10","key":"pbio.3001764.ref052","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":"D Liebschner","year":"2019","journal-title":"Acta Crystallogr D Struct Biol"},{"issue":"Pt 4","key":"pbio.3001764.ref053","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1107\/S0907444911001314","article-title":"REFMAC5 for the refinement of macromolecular crystal structures","volume":"67","author":"GN Murshudov","year":"2011","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 4","key":"pbio.3001764.ref054","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"P Emsley","year":"2010","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 10","key":"pbio.3001764.ref055","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1107\/S0907444909029436","article-title":"electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation","volume":"65","author":"NW Moriarty","year":"2009","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"11","key":"pbio.3001764.ref056","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/nsmb.3115","article-title":"Privateer: software for the conformational validation of carbohydrate structures","volume":"22","author":"J Agirre","year":"2015","journal-title":"Nat Struct Mol Biol"},{"issue":"1","key":"pbio.3001764.ref057","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: Structure visualization for researchers, educators, and developers","volume":"30","author":"EF Pettersen","year":"2021","journal-title":"Protein Sci"},{"key":"pbio.3001764.ref058","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/msb.2011.75","article-title":"Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega","volume":"7","author":"F Sievers","year":"2011","journal-title":"Mol Syst Biol"},{"issue":"Web Server issue","key":"pbio.3001764.ref059","doi-asserted-by":"crossref","first-page":"W320","DOI":"10.1093\/nar\/gku316","article-title":"Deciphering key features in protein structures with the new ENDscript server","volume":"42","author":"X Robert","year":"2014","journal-title":"Nucleic Acids Res"}],"container-title":["PLOS Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3001764","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T10:12:06Z","timestamp":1701079926000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pbio.3001764"}},"subtitle":[],"editor":[{"given":"Raquel L.","family":"Lieberman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pbio.3001764","relation":{},"ISSN":["1545-7885"],"issn-type":[{"value":"1545-7885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]}}}