{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:20:29Z","timestamp":1793658029251,"version":"4.5.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T00:00:00Z","timestamp":1508803200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,10,24]],"date-time":"2017-10-24T00:00:00Z","timestamp":1508803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pompe disease, a rare lysosomal storage disease caused by deficiency of the lysosomal acid \u03b1-glucosidase (GAA), is characterized by glycogen accumulation, triggering severe secondary cellular damage and resulting in progressive motor handicap and premature death. Numerous disease-causing mutations in the <jats:italic>gaa<\/jats:italic> gene have been reported, but the structural effects of the pathological variants were unknown. Here we present the high-resolution crystal structures of recombinant human GAA (rhGAA), the standard care of Pompe disease. These structures portray the unbound form of rhGAA and complexes thereof with active site-directed inhibitors, providing insight into substrate recognition and the molecular framework for the rationalization of the deleterious effects of disease-causing mutations. Furthermore, we report the structure of rhGAA in complex with the allosteric pharmacological chaperone N-acetylcysteine, which reveals the stabilizing function of this chaperone at the structural level.<\/jats:p>","DOI":"10.1038\/s41467-017-01263-3","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T13:00:17Z","timestamp":1508331617000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":310,"title":["Structure of human lysosomal acid \u03b1-glucosidase\u2013a guide for the treatment of Pompe disease"],"prefix":"10.1038","volume":"8","author":[{"given":"V\u00e9ronique","family":"Roig-Zamboni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8211-2297","authenticated-orcid":false,"given":"Beatrice","family":"Cobucci-Ponzano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3586-4322","authenticated-orcid":false,"given":"Roberta","family":"Iacono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-2488","authenticated-orcid":false,"given":"Maria Carmina","family":"Ferrara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Germany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Bourne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giancarlo","family":"Parenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9846-2531","authenticated-orcid":false,"given":"Marco","family":"Moracci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4844-2820","authenticated-orcid":false,"given":"Gerlind","family":"Sulzenbacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,10,24]]},"reference":[{"key":"1263_CR1","doi-asserted-by":"publisher","first-page":"D490","DOI":"10.1093\/nar\/gkt1178","volume":"42","author":"V Lombard","year":"2014","unstructured":"Lombard, V., Golaconda Ramulu, H., Drula, E., Coutinho, P. M. & Henrissat, B. The carbohydrate-active enzymes database (CAZy) in 2013. Nucleic Acids Res. \n                           42, D490\u2013D495 (2014).","journal-title":"Nucleic Acids Res."},{"key":"1263_CR2","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/S0140-6736(08)61555-X","volume":"372","author":"AT van der Ploeg","year":"2008","unstructured":"van der Ploeg, A. T. & Reuser, A. J. Pompe\u2019s disease. Lancet \n                           372, 1342\u20131353 (2008).","journal-title":"Lancet"},{"key":"1263_CR3","doi-asserted-by":"publisher","first-page":"145","DOI":"10.2174\/1566524024605789","volume":"2","author":"N Raben","year":"2002","unstructured":"Raben, N., Plotz, P. & Byrne, B. J. Acid alpha-glucosidase deficiency (glycogenosis type II, Pompe disease). Curr. Mol. Med. \n                           2, 145\u2013166 (2002).","journal-title":"Curr. Mol. Med."},{"key":"1263_CR4","doi-asserted-by":"publisher","first-page":"902","DOI":"10.2174\/138920111795542606","volume":"12","author":"G Parenti","year":"2011","unstructured":"Parenti, G. & Andria, G. Pompe disease: from new views on pathophysiology to innovative therapeutic strategies. Curr. Pharm. Biotechnol. \n                           12, 902\u2013915 (2011).","journal-title":"Curr. Pharm. Biotechnol."},{"key":"1263_CR5","doi-asserted-by":"publisher","first-page":"e448","DOI":"10.1542\/peds.113.5.e448","volume":"113","author":"JM Van den Hout","year":"2004","unstructured":"Van den Hout, J. M. et al. Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics \n                           113, e448\u2013e457 (2004).","journal-title":"Pediatrics"},{"key":"1263_CR6","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.jpeds.2006.02.035","volume":"149","author":"PS Kishnani","year":"2006","unstructured":"Kishnani, P. S. et al. Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease. J. Pediatr. \n                           149, 89\u201397 (2006).","journal-title":"J. Pediatr."},{"key":"1263_CR7","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.jpeds.2009.03.015","volume":"155","author":"LR Chen","year":"2009","unstructured":"Chen, L. R. et al. Reversal of cardiac dysfunction after enzyme replacement in patients with infantile-onset Pompe disease. J. Pediatr. \n                           155, 271\u2013275.e2 (2009).","journal-title":"J. Pediatr."},{"key":"1263_CR8","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1177\/0883073807302598","volume":"22","author":"M Rossi","year":"2007","unstructured":"Rossi, M. et al. Long-term enzyme replacement therapy for pompe disease with recombinant human alpha-glucosidase derived from chinese hamster ovary cells. J. Child. Neurol. \n                           22, 565\u2013573 (2007).","journal-title":"J. Child. Neurol."},{"key":"1263_CR9","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1056\/NEJMoa0909859","volume":"362","author":"AT van der Ploeg","year":"2010","unstructured":"van der Ploeg, A. T. et al. A randomized study of alglucosidase alfa in late-onset Pompe\u2019s disease. N. Engl. J. Med. \n                           362, 1396\u20131406 (2010).","journal-title":"N. Engl. J. Med."},{"key":"1263_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8417-1-6","volume":"1","author":"M Cardone","year":"2008","unstructured":"Cardone, M. et al. Abnormal mannose-6-phosphate receptor trafficking impairs recombinant alpha-glucosidase uptake in Pompe disease fibroblasts. Pathogenetics \n                           1, 6 (2008).","journal-title":"Pathogenetics"},{"key":"1263_CR11","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.ymgme.2009.08.003","volume":"99","author":"PS Kishnani","year":"2010","unstructured":"Kishnani, P. S. et al. Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants. Mol. Genet. Metab. \n                           99, 26\u201333 (2010).","journal-title":"Mol. Genet. Metab."},{"key":"1263_CR12","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.ymthe.2006.08.009","volume":"14","author":"T Fukuda","year":"2006","unstructured":"Fukuda, T. et al. Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease. Mol. Ther. \n                           14, 831\u2013839 (2006).","journal-title":"Mol. Ther."},{"key":"1263_CR13","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1002\/emmm.200900036","volume":"1","author":"G Parenti","year":"2009","unstructured":"Parenti, G. Treating lysosomal storage diseases with pharmacological chaperones: from concept to clinics. EMBO Mol. Med. \n                           1, 268\u2013279 (2009).","journal-title":"EMBO Mol. Med."},{"key":"1263_CR14","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1038\/mt.2015.62","volume":"23","author":"G Parenti","year":"2015","unstructured":"Parenti, G., Andria, G. & Valenzano, K. J. Pharmacological chaperone therapy: preclinical development, clinical translation, and prospects for the treatment of lysosomal storage disorders. Mol. Ther. \n                           23, 1138\u20131148 (2015).","journal-title":"Mol. Ther."},{"key":"1263_CR15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1515\/BC.2008.009","volume":"389","author":"JQ Fan","year":"2008","unstructured":"Fan, J. Q. A counterintuitive approach to treat enzyme deficiencies: use of enzyme inhibitors for restoring mutant enzyme activity. Biol. Chem. \n                           389, 1\u201311 (2008).","journal-title":"Biol. Chem."},{"key":"1263_CR16","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1002\/humu.21121","volume":"30","author":"JJ Flanagan","year":"2009","unstructured":"Flanagan, J. J. et al. The pharmacological chaperone 1-deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidase. Hum. Mutat. \n                           30, 1683\u20131692 (2009).","journal-title":"Hum. Mutat."},{"key":"1263_CR17","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1038\/mt.2009.53","volume":"17","author":"C Porto","year":"2009","unstructured":"Porto, C. et al. The pharmacological chaperone N-butyldeoxynojirimycin enhances enzyme replacement therapy in Pompe disease fibroblasts. Mol. Ther. \n                           17, 964\u2013971 (2009).","journal-title":"Mol. Ther."},{"key":"1263_CR18","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1038\/mt.2012.152","volume":"20","author":"C Porto","year":"2012","unstructured":"Porto, C. et al. Pharmacological enhancement of \u03b1-glucosidase by the allosteric chaperone N-acetylcysteine. Mol. Ther. \n                           20, 2201\u20132211 (2012).","journal-title":"Mol. Ther."},{"key":"1263_CR19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1073\/pnas.93.1.65","volume":"93","author":"JL Van Hove","year":"1996","unstructured":"Van Hove, J. L., Yang, H. W., Wu, J. Y., Brady, R. O. & Chen, Y. T. High-level production of recombinant human lysosomal acid alpha-glucosidase in Chinese hamster ovary cells which targets to heart muscle and corrects glycogen accumulation in fibroblasts from patients with Pompe disease. Proc. Natl Acad. Sci. USA \n                           93, 65\u201370 (1996).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1263_CR20","doi-asserted-by":"publisher","first-page":"6780","DOI":"10.1074\/jbc.M404008200","volume":"280","author":"RJ Moreland","year":"2005","unstructured":"Moreland, R. J. et al. Lysosomal acid alpha-glucosidase consists of four different peptides processed from a single chain precursor. J. Biol. Chem. \n                           280, 6780\u20136791 (2005).","journal-title":"J. Biol. Chem."},{"key":"1263_CR21","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/j.str.2003.10.002","volume":"11","author":"R Linding","year":"2003","unstructured":"Linding, R. et al. Protein disorder prediction: implications for structural proteomics. Structure \n                           11, 1453\u20131459 (2003).","journal-title":"Structure"},{"key":"1263_CR22","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/j.jmb.2007.10.069","volume":"375","author":"L Sim","year":"2008","unstructured":"Sim, L., Quezada-Calvillo, R., Sterchi, E. E., Nichols, B. L. & Rose, D. R. Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. J. Mol. Biol. \n                           375, 782\u2013792 (2008).","journal-title":"J. Mol. Biol."},{"key":"1263_CR23","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1007\/s13238-011-1105-3","volume":"2","author":"L Ren","year":"2011","unstructured":"Ren, L. et al. Structural insight into substrate specificity of human intestinal maltase-glucoamylase. Protein Cell \n                           2, 827\u2013836 (2011).","journal-title":"Protein Cell"},{"key":"1263_CR24","doi-asserted-by":"publisher","first-page":"17763","DOI":"10.1074\/jbc.M109.078980","volume":"285","author":"L Sim","year":"2010","unstructured":"Sim, L. et al. Structural basis for substrate selectivity in human maltase-glucoamylase and sucrase-isomaltase N-terminal domains. J. Biol. Chem. \n                           285, 17763\u201317770 (2010).","journal-title":"J. Biol. Chem."},{"key":"1263_CR25","doi-asserted-by":"crossref","first-page":"13507","DOI":"10.1016\/S0021-9258(18)92727-4","volume":"266","author":"MM Hermans","year":"1991","unstructured":"Hermans, M. M., Kroos, M. A., van Beeumen, J., Oostra, B. A. & Reuser, A. J. Human lysosomal alpha-glucosidase. characterization of the catalytic site. J. Biol. Chem. \n                           266, 13507\u201313512 (1991).","journal-title":"J. Biol. Chem."},{"key":"1263_CR26","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1074\/jbc.M410468200","volume":"280","author":"AL Lovering","year":"2005","unstructured":"Lovering, A. L., Lee, S. S., Kim, Y. W., Withers, S. G. & Strynadka, N. C. Mechanistic and structural analysis of a family 31 alpha-glycosidase and its glycosyl-enzyme intermediate. J. Biol. Chem. \n                           280, 2105\u20132115 (2005).","journal-title":"J. Biol. Chem."},{"key":"1263_CR27","doi-asserted-by":"publisher","first-page":"2202","DOI":"10.1021\/ja057904a","volume":"128","author":"YW Kim","year":"2006","unstructured":"Kim, Y. W. et al. Expanding the thioglycoligase strategy to the synthesis of alpha-linked thioglycosides allows structural investigation of the parent enzyme\/substrate complex. J. Am. Chem. Soc. \n                           128, 2202\u20132203 (2006).","journal-title":"J. Am. Chem. Soc."},{"key":"1263_CR28","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1016\/j.ymthe.2017.02.017","volume":"25","author":"P Kishnani","year":"2017","unstructured":"Kishnani, P. et al. Duvoglustat HCl increases systemic and tissue exposure of active acid \u03b1-glucosidase in pompe patients co-administered with alglucosidase \u03b1. Mol. Ther. \n                           25, 1199\u20131208 (2017).","journal-title":"Mol. Ther."},{"key":"1263_CR29","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1002\/cmdc.201200309","volume":"7","author":"C Bruckmann","year":"2012","unstructured":"Bruckmann, C., Repo, H., Kuokkanen, E., Xhaard, H. & Heikinheimo, P. Systematic structure-activity study on potential chaperone lead compounds for acid \u03b1-glucosidase. ChemMedChem. \n                           7, 1943\u20131953 (2012).","journal-title":"ChemMedChem."},{"key":"1263_CR30","doi-asserted-by":"publisher","DOI":"10.1042\/bj3210557","volume":"321","author":"GJ Davies","year":"1997","unstructured":"Davies, G. J., Wilson, K. S. & Henrissat, B. Nomenclature for sugar-binding subsites in glycosyl hydrolases. Biochem. J. \n                           321, 557 (1997).","journal-title":"Biochem. J."},{"key":"1263_CR31","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1021\/bi9016457","volume":"49","author":"L Sim","year":"2010","unstructured":"Sim, L. et al. New glucosidase inhibitors from an ayurvedic herbal treatment for type 2 diabetes: structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata. Biochemistry \n                           49, 443\u2013451 (2010).","journal-title":"Biochemistry"},{"key":"1263_CR32","doi-asserted-by":"publisher","first-page":"3939","DOI":"10.1096\/fj.10-156257","volume":"24","author":"K Tan","year":"2010","unstructured":"Tan, K. et al. Novel \u03b1-glucosidase from human gut microbiome: substrate specificities and their switch. FASEB J. \n                           24, 3939\u20133949 (2010).","journal-title":"FASEB J."},{"key":"1263_CR33","doi-asserted-by":"publisher","first-page":"26764","DOI":"10.1074\/jbc.M113.485896","volume":"288","author":"HJ Rozeboom","year":"2013","unstructured":"Rozeboom, H. J. et al. Crystal structure of \u03b1\u22121,4-glucan lyase, a unique glycoside hydrolase family member with a novel catalytic mechanism. J. Biol. Chem. \n                           288, 26764\u201326774 (2013).","journal-title":"J. Biol. Chem."},{"key":"1263_CR34","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.4155\/fmc.14.40","volume":"6","author":"G Parenti","year":"2014","unstructured":"Parenti, G., Moracci, M., Fecarotta, S. & Andria, G. Pharmacological chaperone therapy for lysosomal storage diseases. Future Med. Chem. \n                           6, 1031\u20131045 (2014).","journal-title":"Future Med. Chem."},{"key":"1263_CR35","doi-asserted-by":"publisher","first-page":"2004","DOI":"10.1038\/mt.2014.138","volume":"22","author":"G Parenti","year":"2014","unstructured":"Parenti, G. et al. A chaperone enhances blood \u03b1-glucosidase activity in Pompe disease patients treated with enzyme replacement therapy. Mol. Ther. \n                           22, 2004\u20132012 (2014).","journal-title":"Mol. Ther."},{"key":"1263_CR36","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/nbt0596-595","volume":"14","author":"C Mattos","year":"1996","unstructured":"Mattos, C. & Ringe, D. Locating and characterizing binding sites on proteins. Nat. Biotechnol. \n                           14, 595\u2013599 (1996).","journal-title":"Nat. Biotechnol."},{"key":"1263_CR37","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1107\/S0907444909047337","volume":"66","author":"W Kabsch","year":"2010","unstructured":"Kabsch, W. XDS. Acta. Crystallogr. D. Biol. Crystallogr. \n                           66, 125\u2013132 (2010).","journal-title":"Acta. Crystallogr. D. Biol. Crystallogr."},{"key":"1263_CR38","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1107\/S0907444910045749","volume":"67","author":"MD Winn","year":"2011","unstructured":"Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta. Crystallogr. D. Biol. Crystallogr. \n                           67, 235\u2013242 (2011).","journal-title":"Acta. Crystallogr. D. Biol. Crystallogr."},{"key":"1263_CR39","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1107\/S0907444913000061","volume":"69","author":"PR Evans","year":"2013","unstructured":"Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta. Crystallogr. D Biol. Crystallogr. \n                           69, 1204\u20131214 (2013).","journal-title":"Acta. Crystallogr. D Biol. Crystallogr."},{"key":"1263_CR40","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1107\/S0021889807021206","volume":"40","author":"AJ McCoy","year":"2007","unstructured":"McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. \n                           40, 658\u2013674 (2007).","journal-title":"J. Appl. Crystallogr."},{"key":"1263_CR41","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1107\/S0907444906022116","volume":"62","author":"K Cowtan","year":"2006","unstructured":"Cowtan, K. The Buccaneer software for automated model building. 1. Tracing protein chains. Acta. Crystallogr. D Biol. Crystallogr. \n                           62, 1002\u20131011 (2006).","journal-title":"Acta. Crystallogr. D Biol. Crystallogr."},{"key":"1263_CR42","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1107\/S0907444996012255","volume":"53","author":"GN Murshudov","year":"1997","unstructured":"Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta. Crystallogr. D Biol. Crystallogr. \n                           53, 240\u2013255 (1997).","journal-title":"Acta. Crystallogr. D Biol. Crystallogr."},{"key":"1263_CR43","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta. Crystallogr. D Biol. Crystallogr. \n                           66, 486\u2013501 (2010).","journal-title":"Acta. Crystallogr. D Biol. Crystallogr."},{"key":"1263_CR44","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1107\/S0907444909042073","volume":"66","author":"VB Chen","year":"2010","unstructured":"Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta. Crystallogr. D Biol. Crystallogr. \n                           66, 12\u201321 (2010).","journal-title":"Acta. Crystallogr. D Biol. Crystallogr."},{"key":"1263_CR45","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1093\/nar\/gkh340","volume":"32","author":"RC Edgar","year":"2004","unstructured":"Edgar, R. C. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. \n                           32, 1792\u20131797 (2004).","journal-title":"Nucleic Acids Res."},{"key":"1263_CR46","doi-asserted-by":"publisher","first-page":"W320","DOI":"10.1093\/nar\/gku316","volume":"42","author":"X Robert","year":"2014","unstructured":"Robert, X. & Gouet, P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. \n                           42, W320\u2013W324 (2014).","journal-title":"Nucleic Acids Res."},{"key":"1263_CR47","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1038\/nprot.2007.321","volume":"2","author":"FH Niesen","year":"2007","unstructured":"Niesen, F. H., Berglund, H. & Vedadi, M. The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat. Protoc. \n                           2, 2212\u20132221 (2007).","journal-title":"Nat. Protoc."},{"key":"1263_CR48","volume":"91","author":"M Vivoli","year":"2014","unstructured":"Vivoli, M., Novak, H. R., Littlechild, J. A. & Harmer, N. J. Determination of protein-ligand interactions using differential scanning fluorimetry. J. Vis. Exp. 91, 51809 (2014).","journal-title":"J. Vis. Exp."},{"key":"1263_CR49","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0021-9258(19)50870-5","volume":"195","author":"M SmogyiI","year":"1952","unstructured":"SmogyiI, M. Notes on sugar determination. J. Biol. Chem. \n                           195, 19\u201323 (1952).","journal-title":"J. Biol. Chem."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-017-01263-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-017-01263-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-017-01263-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T21:45:28Z","timestamp":1671745528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-017-01263-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,24]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["1263"],"URL":"https:\/\/doi.org\/10.1038\/s41467-017-01263-3","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,24]]},"assertion":[{"value":"28 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1111"}}