{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T19:26:02Z","timestamp":1784921162112,"version":"3.55.0"},"reference-count":58,"publisher":"Elsevier BV","issue":"34","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":2261,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK069764"],"award-info":[{"award-number":["R01 DK069764"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2014,8]]},"DOI":"10.1074\/jbc.m114.572040","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T00:19:48Z","timestamp":1404778788000},"page":"23683-23692","source":"Crossref","is-referenced-by-count":21,"title":["Deciphering a Molecular Mechanism of Neonatal Diabetes Mellitus by the Chemical Synthesis of a Protein Diastereomer, [d-AlaB8]Human Proinsulin"],"prefix":"10.1016","volume":"289","author":[{"given":"Michal","family":"Avital-Shmilovici","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Whittaker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.H.","family":"Kent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1074\/jbc.M114.572040_bib1","doi-asserted-by":"crossref","first-page":"F39","DOI":"10.1136\/fn.76.1.F39","article-title":"Aetiopathology and genetic basis of neonatal diabetes","volume":"76","author":"Shield","year":"1997","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed"},{"key":"10.1074\/jbc.M114.572040_bib2","doi-asserted-by":"crossref","first-page":"15040","DOI":"10.1073\/pnas.0707291104","article-title":"Insulin gene mutations as a cause of permanent neonatal diabetes","volume":"104","author":"St\u00f8y","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"10.1074\/jbc.M114.572040_bib3","first-page":"2148","article-title":"Seven mutations in the human insulin gene linked to permanent neonatal\/infancy-onset diabetes mellitus","volume":"118","author":"Colombo","year":"2008","journal-title":"J. Clin. Investig"},{"key":"10.1074\/jbc.M114.572040_bib4","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.2337\/db07-1405","article-title":"Mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood","volume":"57","author":"Edghill","year":"2008","journal-title":"Diabetes"},{"key":"10.1074\/jbc.M114.572040_bib5","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.2337\/db07-1467","article-title":"Mutations in the insulin gene can cause MODY and autoantibody-negative type 1 diabetes","volume":"57","author":"Molven","year":"2008","journal-title":"Diabetes"},{"key":"10.1074\/jbc.M114.572040_bib6","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1016\/j.febslet.2013.04.044","article-title":"Diabetes mellitus due to the toxic misfolding of proinsulin variants","volume":"587","author":"Weiss","year":"2013","journal-title":"FEBS Lett"},{"key":"10.1074\/jbc.M114.572040_bib7","doi-asserted-by":"crossref","first-page":"4984","DOI":"10.1021\/bi048025o","article-title":"Chiral mutagenesis of insulin: foldability and function are inversely regulated by a stereospecific switch in the B chain","volume":"44","author":"Nakagawa","year":"2005","journal-title":"Biochemistry"},{"key":"10.1074\/jbc.M114.572040_bib8","doi-asserted-by":"crossref","first-page":"24900","DOI":"10.1074\/jbc.M602691200","article-title":"Toward the active conformation of insulin: stereospecific modulation of a structural switch in the B chain","volume":"281","author":"Hua","year":"2006","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.M114.572040_bib9","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/354238a0","article-title":"Receptor binding redefined by a structural switch in a mutant human insulin","volume":"354","author":"Hua","year":"1991","journal-title":"Nature"},{"key":"10.1074\/jbc.M114.572040_bib10","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1038\/338594a0","article-title":"Phenol stabilizes more helix in a new symmetrical zinc insulin hexamer","volume":"338","author":"Derewenda","year":"1989","journal-title":"Nature"},{"key":"10.1074\/jbc.M114.572040_bib11","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1006\/jmbi.1996.0648","article-title":"Mapping the functional surface of insulin by design: structure and function of a novel A-chain analogue","volume":"264","author":"Hua","year":"1996","journal-title":"J. Mol. Biol"},{"key":"10.1074\/jbc.M114.572040_bib12","doi-asserted-by":"crossref","first-page":"8836","DOI":"10.1021\/bi960292+","article-title":"Solution structure of an engineered insulin monomer at neutral pH","volume":"35","author":"Olsen","year":"1996","journal-title":"Biochemistry"},{"key":"10.1074\/jbc.M114.572040_bib13","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1098\/rstb.1988.0058","article-title":"The structure of 2Zn pig insulin crystals at 1.5-\u00c5 resolution","volume":"319","author":"Baker","year":"1988","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci"},{"key":"10.1074\/jbc.M114.572040_bib14","doi-asserted-by":"crossref","first-page":"22386","DOI":"10.1074\/jbc.M603547200","article-title":"Chiral mutagenesis of insulin: contribution of the B20-B23 \u03b2-turn to activity and stability","volume":"281","author":"Nakagawa","year":"2006","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.M114.572040_bib15","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1006\/scdb.1999.0319","article-title":"Protein disulfide isomerase: the multifunctional redox chaperone of the endoplasmic reticulum","volume":"10","author":"Noiva","year":"1999","journal-title":"Semin. Cell Dev. Biol"},{"key":"10.1074\/jbc.M114.572040_bib16","first-page":"407","article-title":"Isomerase and chaperone activities of protein disulfide isomerase are both required for its function as a foldase","volume":"63","author":"Wang","year":"1998","journal-title":"Biochemistry"},{"key":"10.1074\/jbc.M114.572040_bib17","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0962-8924(00)01745-1","article-title":"Pathways for protein disulphide bond formation","volume":"10","author":"Frand","year":"2000","journal-title":"Trends Cell Biol"},{"key":"10.1074\/jbc.M114.572040_bib18","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1126\/science.290.5496.1571","article-title":"Biochemical basis of oxidative protein folding in the endoplasmic reticulum","volume":"290","author":"Tu","year":"2000","journal-title":"Science"},{"key":"10.1074\/jbc.M114.572040_bib19","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1074\/jbc.M107832200","article-title":"Catalytic activity and chaperone function of human protein-disulfide isomerase are required for the efficient refolding of proinsulin","volume":"277","author":"Winter","year":"2002","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.M114.572040_bib20","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1172\/JCI107845","article-title":"The interactions of proinsulin with insulin receptors on the plasma membrane of the liver","volume":"54","author":"Freychet","year":"1974","journal-title":"J. Clin. Investig"},{"key":"10.1074\/jbc.M114.572040_bib21","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1021\/jo00408a022","article-title":"A new synthetic route to tert-butyloxycarbonylaminoacyl-4-(oxymethyl)phenylacetamidomethyl-resin, an improved support for solid-phase peptide synthesis","volume":"43","author":"Mitchell","year":"1978","journal-title":"J. Org. Chem"},{"key":"10.1074\/jbc.M114.572040_bib22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10989-006-9059-7","article-title":"In situ neutralization in Boc-chemistry solid phase peptide synthesis","volume":"13","author":"Schn\u00f6lzer","year":"2007","journal-title":"Int. J. Pept. Res. Ther"},{"key":"10.1074\/jbc.M114.572040_bib23","doi-asserted-by":"crossref","first-page":"10068","DOI":"10.1073\/pnas.96.18.10068","article-title":"Protein synthesis by native chemical ligation: expanded scope by using straightforward methodology","volume":"96","author":"Hackeng","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"10.1074\/jbc.M114.572040_bib24","doi-asserted-by":"crossref","first-page":"6640","DOI":"10.1021\/ja058344i","article-title":"Insights into the mechanism and catalysis of the native chemical ligation reaction","volume":"128","author":"Johnson","year":"2006","journal-title":"J. Am. Chem. Soc"},{"key":"10.1074\/jbc.M114.572040_bib25","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S1074-5521(01)00044-8","article-title":"Covalent capture: a new tool for the purification of synthetic and recombinant polypeptides","volume":"8","author":"Villain","year":"2001","journal-title":"Chem. Biol"},{"key":"10.1074\/jbc.M114.572040_bib26","doi-asserted-by":"crossref","first-page":"8177","DOI":"10.1039\/c0cc03141k","article-title":"Total chemical synthesis of human proinsulin","volume":"46","author":"Luisier","year":"2010","journal-title":"Chem. Commun. (Camb)"},{"key":"10.1074\/jbc.M114.572040_bib27","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/S1046-5928(02)00643-5","article-title":"Expression, purification, and PC1-mediated processing of (H10D, P28K, and K29P)-human proinsulin","volume":"27","author":"Mackin","year":"2003","journal-title":"Protein Expr. Purif"},{"key":"10.1074\/jbc.M114.572040_bib28","doi-asserted-by":"crossref","first-page":"20932","DOI":"10.1074\/jbc.M411320200","article-title":"Characterization of the functional insulin binding epitopes of the full-length insulin receptor","volume":"280","author":"Whittaker","year":"2005","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.M114.572040_bib29","doi-asserted-by":"crossref","first-page":"5040","DOI":"10.1074\/jbc.M109.062992","article-title":"Contribution of residue B5 to the folding and function of insulin and IGF-I: constraints and fine-tuning in the evolution of a protein family","volume":"285","author":"Sohma","year":"2010","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.M114.572040_bib30","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1002\/anie.200353540","article-title":"A one-pot total synthesis of crambin","volume":"43","author":"Bang","year":"2004","journal-title":"Angew. Chem. Int. Ed. Engl"},{"key":"10.1074\/jbc.M114.572040_bib31","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1126\/science.7973629","article-title":"Synthesis of proteins by native chemical ligation","volume":"266","author":"Dawson","year":"1994","journal-title":"Science"},{"key":"10.1074\/jbc.M114.572040_bib32","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1039\/B700141J","article-title":"Total chemical synthesis of proteins","volume":"38","author":"Kent","year":"2009","journal-title":"Chem. Soc. Rev"},{"key":"10.1074\/jbc.M114.572040_bib33","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0003-2697(02)00287-7","article-title":"Renaturation of human proinsulin: a study on refolding and conversion to insulin","volume":"310","author":"Winter","year":"2002","journal-title":"Anal. Biochem"},{"key":"10.1074\/jbc.M114.572040_bib34","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1126\/science.181.4096.223","article-title":"Principles the govern the folding of protein chains","volume":"181","author":"Anfinsen","year":"1973","journal-title":"Science"},{"key":"10.1074\/jbc.M114.572040_bib35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/nsb0197-10","article-title":"From Levinthal to pathways to funnels","volume":"4","author":"Dill","year":"1997","journal-title":"Nat. Struct. Biol"},{"key":"10.1074\/jbc.M114.572040_bib36","doi-asserted-by":"crossref","first-page":"S69","DOI":"10.1016\/S1359-0278(97)00067-9","article-title":"The Levinthal paradox: yesterday and today","volume":"2","author":"Karplus","year":"1997","journal-title":"Fold. Des"},{"key":"10.1074\/jbc.M114.572040_bib37","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/369248a0","article-title":"How does a protein fold?","volume":"369","author":"Sali","year":"1994","journal-title":"Nature"},{"key":"10.1074\/jbc.M114.572040_bib38","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev.physchem.58.032806.104449","article-title":"Understanding protein evolution: from protein physics to Darwinian selection","volume":"59","author":"Zeldovich","year":"2008","journal-title":"Annu. Rev. Phys. Chem"},{"key":"10.1074\/jbc.M114.572040_bib39","doi-asserted-by":"crossref","first-page":"11305","DOI":"10.1073\/pnas.96.20.11305","article-title":"Prediction of protein-folding mechanisms from free-energy landscapes derived from native structures","volume":"96","author":"Alm","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"10.1074\/jbc.M114.572040_bib40","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/bies.950140310","article-title":"What the papers say: protein folding pathways determined using disulphide bonds","volume":"14","author":"Creighton","year":"1992","journal-title":"Bioessays"},{"key":"10.1074\/jbc.M114.572040_bib41","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.sbi.2007.11.007","article-title":"Combining experiment and simulation in protein folding: closing the gap for small model systems","volume":"18","author":"Schaeffer","year":"2008","journal-title":"Curr. Opin. Struct. Biol"},{"key":"10.1074\/jbc.M114.572040_bib42","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1146\/annurev.biochem.75.101304.123901","article-title":"Protein misfolding, functional amyloid, and human disease","volume":"75","author":"Chiti","year":"2006","journal-title":"Annu. Rev. Biochem"},{"key":"10.1074\/jbc.M114.572040_bib43","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/nature02261","article-title":"Protein folding and misfolding","volume":"426","author":"Dobson","year":"2003","journal-title":"Nature"},{"key":"10.1074\/jbc.M114.572040_bib44","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.sbi.2009.12.009","article-title":"Structure-based design of kinetic stabilizers that ameliorate the transthyretin amyloidoses","volume":"20","author":"Connelly","year":"2010","journal-title":"Curr. Opin. Struct. Biol"},{"key":"10.1074\/jbc.M114.572040_bib45","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1172\/JCI0215020","article-title":"Proteotoxicity in the endoplasmic reticulum: lessons from the Akita diabetic mouse","volume":"109","author":"Ron","year":"2002","journal-title":"J. Clin. Invest"},{"key":"10.1074\/jbc.M114.572040_bib46","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.ceb.2006.06.005","article-title":"Endoplasmic reticulum stress in health and disease","volume":"18","author":"Zhao","year":"2006","journal-title":"Curr. Opin. Cell Biol"},{"key":"10.1074\/jbc.M114.572040_bib47","first-page":"266","article-title":"Endoplasmic reticulum stress and pancreatic \u03b2-cell death","volume":"22","author":"Fonseca","year":"2011","journal-title":"Trends Endocrinol. Metab"},{"key":"10.1074\/jbc.M114.572040_bib48","doi-asserted-by":"crossref","first-page":"35259","DOI":"10.1074\/jbc.M109.046888","article-title":"Crystal structure of a \u201cnonfoldable\u201d insulin: impaired folding efficiency despite native activity","volume":"284","author":"Liu","year":"2009","journal-title":"J. Biol. Chem"},{"key":"10.1074\/jbc.M114.572040_bib49","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1126\/science.154.3756.1509","article-title":"Synthesis of insulin","volume":"154","author":"Katsoyannis","year":"1966","journal-title":"Science"},{"key":"10.1074\/jbc.M114.572040_bib50","doi-asserted-by":"crossref","first-page":"16313","DOI":"10.1021\/ja9052398","article-title":"Biomimetic synthesis of lispro insulin via a chemically synthesized \u201cmini-proinsulin\u201d prepared by oxime-forming ligation","volume":"131","author":"Sohma","year":"2009","journal-title":"J. Am. Chem. Soc"},{"key":"10.1074\/jbc.M114.572040_bib51","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/261166a0","article-title":"Structure of insulin in 4-zinc insulin","volume":"261","author":"Bentley","year":"1976","journal-title":"Nature"},{"key":"10.1074\/jbc.M114.572040_bib52","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrd917","article-title":"Structural biology of insulin and IGF1 receptors: implications for drug design","volume":"1","author":"De Meyts","year":"2002","journal-title":"Nat. Rev. Drug Discov"},{"key":"10.1074\/jbc.M114.572040_bib53","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.tem.2010.07.001","article-title":"Proinsulin misfolding and diabetes: mutant INS gene-induced diabetes of youth","volume":"21","author":"Liu","year":"2010","journal-title":"Trends Endocrinol. Metab"},{"key":"10.1074\/jbc.M114.572040_bib54","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1056\/NEJM199309303291401","article-title":"The Effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus","volume":"329","author":"DCCT","year":"1993","journal-title":"N. Engl. J. Med"},{"key":"10.1074\/jbc.M114.572040_bib55","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1056\/NEJMoa052187","article-title":"Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes","volume":"353","author":"Nathan","year":"2005","journal-title":"N. Engl. J. Med"},{"key":"10.1074\/jbc.M114.572040_bib56","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.sbi.2005.01.002","article-title":"Natively unfolded proteins","volume":"15","author":"Fink","year":"2005","journal-title":"Curr. Opin. Struct. Biol"},{"key":"10.1074\/jbc.M114.572040_bib57","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1021\/ja311408y","article-title":"Fully convergent chemical synthesis of ester insulin: determination of the high resolution x-ray structure by racemic protein crystallography","volume":"135","author":"Avital-Shmilovici","year":"2013","journal-title":"J. Am. Chem. Soc"},{"key":"10.1074\/jbc.M114.572040_bib58","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nature11781","article-title":"How insulin engages its primary binding site on the insulin receptor","volume":"493","author":"Menting","year":"2013","journal-title":"Nature"}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820320421?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820320421?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1074\/jbc.M114.572040","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T04:44:45Z","timestamp":1641271485000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925820320421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":58,"journal-issue":{"issue":"34","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["S0021925820320421"],"URL":"https:\/\/doi.org\/10.1074\/jbc.m114.572040","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2014,8]]}}}