{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:17:09Z","timestamp":1790421429400,"version":"4.1.0"},"reference-count":45,"publisher":"American Chemical Society (ACS)","issue":"23","license":[{"start":{"date-parts":[[2015,6,5]],"date-time":"2015-06-05T00:00:00Z","timestamp":1433462400000},"content-version":"vor","delay-in-days":365,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The location of the Trp radical and the catalytic function of the [Fe(IV)\u2550O Trp191\u2022+] intermediate in cytochrome c peroxidase (CcP) are well-established; however, the unambiguous identification of the site(s) for the formation of tyrosyl radical(s) and their possible biological roles remain elusive. We have now performed a systematic investigation of the location and reactivity of the Tyr radical(s) using multifrequency Electron Paramagnetic Resonance (EPR) spectroscopy combined with multiple-site Trp\/Tyr mutations in CcP. Two tyrosines, Tyr71 and Tyr236, were identified as those contributing primarily to the EPR spectrum of the tyrosyl radical, recorded at 9 and 285 GHz. The EPR characterization also showed that the heme distal-side Trp51 is involved in the intramolecular electron transfer between Tyr71 and the heme and that formation of Tyr71\u2022 and Tyr236\u2022 is independent of the [Fe(IV)\u2550O Trp191\u2022+] intermediate. Tyr71 is located in an optimal position to mediate the oxidation of substrates binding at a site, more than 20 \u00c5 from the heme, which has been reported recently in the crystal structures of CcP with bound guaicol and phenol [Murphy, E. J., et al. (2012) FEBS J. 279, 1632\u20131639]. The possibility of discriminating the radical intermediates by their EPR spectra allowed us to identify Tyr71\u2022 as the reactive species with the guaiacol substrate. Our assignment of the surface-exposed Tyr236 as the other radical site agrees well with previous studies based on MNP labeling and protein cross-linking [Tsaprailis, G., and English, A. M. (2003) JBIC, J. Biol. Inorg. Chem. 8, 248\u2013255] and on its covalent modification upon reaction of W191G CcP with 2-aminotriazole [Musah, R. A., and Goodin, D. B. (1997) Biochemistry 36, 11665\u201311674]. Accordingly, while Tyr71 acts as a true reactive intermediate for the oxidation of certain small substrates that bind at a site remote from the heme, the surface-exposed Tyr236 would be more likely related to oxidative stress signaling, as previously proposed. Our findings reinforce the view that CcP is the monofunctional peroxidase that most closely resembles its ancestor enzymes, the catalase-peroxidases, in terms of the higher complexity of the peroxidase reaction [Colin, J., et al. (2009) J. Am. Chem. Soc. 131, 8557\u20138563]. The strategy used to identify the elusive Tyr radical sites in CcP may be applied to other heme enzymes containing a large number of Tyr and Trp residues and for which Tyr (or Trp) radicals have been proposed to be involved in their peroxidase or peroxidase-like reaction.<\/jats:p>","DOI":"10.1021\/bi500353p","type":"journal-article","created":{"date-parts":[[2014,6,5]],"date-time":"2014-06-05T14:12:31Z","timestamp":1401977551000},"page":"3781-3789","source":"Crossref","is-referenced-by-count":29,"title":["Identifying the Elusive Sites of Tyrosyl Radicals\nin Cytochrome\n                    <i>c<\/i>\n                    Peroxidase: Implications for Oxidation of Substrates Bound at a Site Remote\nfrom the Heme"],"prefix":"10.1021","volume":"53","author":[{"given":"Kyle D.","family":"Miner","sequence":"first","affiliation":[{"name":"University of Illinois at Urbana-Champaign , , , ,","place":["Urbana, Illinois, United States, 61801"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Pfister","sequence":"additional","affiliation":[{"name":"University of Illinois at Urbana-Champaign , , , ,","place":["Urbana, Illinois, United States, 61801"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parisa","family":"Hosseinzadeh","sequence":"additional","affiliation":[{"name":"University of Illinois at Urbana-Champaign , , , ,","place":["Urbana, Illinois, United States, 61801"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadime","family":"Karaduman","sequence":"additional","affiliation":[{"name":"CNRS, Unite\u0301 de Recherche Mixte CNRS\/CEA\/Universite\u0301 Paris-Sud (UMR 8221), Laboratoire de Bioe\u0301nerge\u0301tique, Me\u0301talloprote\u0301ines et Stress. Centre d\u2019Etudes de Saclay, iBiTec-S , ,","place":["Gif-sur-Yvette, France, 91191"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda J.","family":"Donald","sequence":"additional","affiliation":[{"name":"University of Manitoba , , , ,","place":["Winnipeg, MB, Canada, R3T 2N2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Loewen","sequence":"additional","affiliation":[{"name":"University of Manitoba , , , ,","place":["Winnipeg, MB, Canada, R3T 2N2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"University of Illinois at Urbana-Champaign , , , ,","place":["Urbana, Illinois, United States, 61801"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anabella","family":"Ivancich","sequence":"additional","affiliation":[{"name":"CNRS, Unite\u0301 de Recherche Mixte CNRS\/CEA\/Universite\u0301 Paris-Sud (UMR 8221), Laboratoire de Bioe\u0301nerge\u0301tique, Me\u0301talloprote\u0301ines et Stress. Centre d\u2019Etudes de Saclay, iBiTec-S , ,","place":["Gif-sur-Yvette, France, 91191"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2014,6,5]]},"reference":[{"key":"2026090117334720700_cit1","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1021\/cr9400875","article-title":"Protein radicals\nin enzyme catalysis","volume":"98","author":"Stubbe","year":"1998","journal-title":"Chem. Rev."},{"key":"2026090117334720700_cit2","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.1016\/j.ccr.2012.03.032","article-title":"Electron hopping\nthrough proteins","volume":"256","author":"Warren","year":"2012","journal-title":"Coord. Chem. Rev."},{"key":"2026090117334720700_cit3","volume-title":"Heme Peroxidases","author":"Dunford","year":"1999"},{"key":"2026090117334720700_cit4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.abb.2010.02.008","article-title":"Thirty\nyears of heme peroxidase structural biology","volume":"500","author":"Poulos","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"2026090117334720700_cit5","doi-asserted-by":"crossref","first-page":"3919","DOI":"10.1021\/cr400415k","article-title":"Heme enzyme\nstructure and function","volume":"114","author":"Poulos","year":"2014","journal-title":"Chem. Rev."},{"key":"2026090117334720700_cit6","doi-asserted-by":"crossref","first-page":"6243","DOI":"10.1021\/bi00417a008","article-title":"Tryptophan-191\u2192Phenylalanine,\na proximal-side mutation in yeast cytochrome c peroxidase\nthat strongly affects the kinetics of ferrocytochrome c oxidation","volume":"27","author":"Mauro","year":"1988","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit7","doi-asserted-by":"crossref","first-page":"7992","DOI":"10.1021\/bi00446a004","article-title":"Detection of an oxyferryl\nporphyrin \u03c0-cation-radical intermediate in the reaction between\nhydrogen peroxide and a mutant yeast cytochrome c peroxidase. Evidence for tryptophan-191 involvement in the radical\nsite of Compound I","volume":"28","author":"Erman","year":"1989","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit8","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1126\/science.2549632","article-title":"Identification by ENDOR\nof Trp191 as the free-radical site in cytochrome c peroxidase Compound\nES","volume":"245","author":"Sivaraja","year":"1989","journal-title":"Science"},{"key":"2026090117334720700_cit9","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0167-4838(02)00317-5","article-title":"Yeast cytochrome c peroxidase: Mechanistic studies\nvia protein engineering","volume":"1597","author":"Erman","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"2026090117334720700_cit10","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1016\/j.bbabio.2011.07.010","article-title":"The\ncomplex of cytochrome c and cytochrome\nc peroxidase: The end of the road?","volume":"1807","author":"Volkov","year":"2011","journal-title":"Biochim.\nBiophys. Acta"},{"key":"2026090117334720700_cit11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.abb.2010.02.015","article-title":"An analysis\nof substrate binding interactions in the heme peroxidase enzymes:\nA structural perspective","volume":"500","author":"Gumiero","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"2026090117334720700_cit12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/bi8020263","article-title":"Replacement\nof an Electron Transfer\nPathway in Cytochrome c Peroxidase with a Surrogate Peptide","volume":"48","author":"Putnam","year":"2009","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit13","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1021\/bi00221a036","article-title":"Compound I radical in site-directed\nmutants of cytochrome c peroxidase as probed by electron paramagnetic\nresonance and electron-nuclear double resonance","volume":"30","author":"Fishel","year":"1991","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit14","doi-asserted-by":"crossref","first-page":"4430","DOI":"10.1021\/bi00067a036","article-title":"Comprehensive explanation\nof the anomalous EPR spectra of wild-type and mutant cytochrome c peroxidase Compound ES","volume":"32","author":"Housseman","year":"1993","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit15","doi-asserted-by":"crossref","first-page":"9033","DOI":"10.1021\/ja00140a021","article-title":"Compound\nES of cytochrome c peroxidase\ncontains a Trp \u03c0-cation radical: Characterization by CW and\nPulsed Q-band ENDOR","volume":"117","author":"Huyett","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"2026090117334720700_cit16","doi-asserted-by":"crossref","first-page":"5050","DOI":"10.1021\/ja0036514","article-title":"Multifrequency high-field\nEPR study of the tryptophanyl and tyrosyl radical intermediates in\nwild-type and the W191G mutant of cytochrome c peroxidase","volume":"123","author":"Ivancich","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"2026090117334720700_cit17","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/S0021-9258(18)89739-3","article-title":"Powder and single-crystal electron paramagnetic resonance\nstudies of yeast cytochrome c peroxidase and its\nperoxide compound, Compound ES","volume":"260","author":"Hori","year":"1985","journal-title":"J. Biol. Chem."},{"key":"2026090117334720700_cit18","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s00775-002-0407-6","article-title":"Different pathways\nof radical translocation in yeast\ncytochrome c peroxidase and its W191F mutant on reaction with H2O2 suggest an antioxidant role","volume":"8","author":"Tsaprailis","year":"2003","journal-title":"JBIC, J. Biol. Inorg. Chem."},{"key":"2026090117334720700_cit19","doi-asserted-by":"crossref","first-page":"11665","DOI":"10.1021\/bi9708038","article-title":"Introduction of novel substrate oxidation into cytochrome\nc peroxidase by cavity complementation: Oxidation of 2-aminothiazole\nand covalent modification of the enzyme","volume":"36","author":"Musah","year":"1997","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit20","doi-asserted-by":"crossref","first-page":"13507","DOI":"10.1021\/bi026122g","article-title":"Radical\nformation at Tyr39 and Tyr153 following reaction\nof yeast cytochrome c peroxidase with hydrogen peroxide","volume":"41","author":"Zhang","year":"2002","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit21","doi-asserted-by":"crossref","first-page":"8655","DOI":"10.1021\/ja0291888","article-title":"Scavenging with TEMPO\u2022 to identify\npeptide- and protein-based radicals by mass spectrometry: Advantages\nof spin scavenging over spin trapping","volume":"125","author":"Wright","year":"2003","journal-title":"J. Am.\nChem. Soc."},{"key":"2026090117334720700_cit22","doi-asserted-by":"crossref","first-page":"15954","DOI":"10.1021\/ja075108u","article-title":"Two [Fe(IV)\u2550O\nTrp\u2022] intermediates in M. tuberculosis catalase-peroxidase discriminated by multifrequency (9\u2013285\nGHz) EPR spectroscopy: Reactivity toward isoniazid","volume":"129","author":"Singh","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"2026090117334720700_cit23","doi-asserted-by":"crossref","first-page":"8557","DOI":"10.1021\/ja901402v","article-title":"Distinct role\nof specific tryptophans in facilitating electron transfer or as [Fe(IV)\u2550O\nTrp\u2022] intermediates in the peroxidase reaction of Burkholderia pseudomallei catalase-peroxidase: A multifrequency\nEPR spectroscopy investigation","volume":"131","author":"Colin","year":"2009","journal-title":"J. Am. Chem.\nSoc."},{"key":"2026090117334720700_cit24","doi-asserted-by":"crossref","first-page":"26662","DOI":"10.1074\/jbc.M110.139428","article-title":"Isonicotinic\nacid hydrazide conversion\nto isonicotinyl-NAD by catalase-peroxidases","volume":"285","author":"Wiseman","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2026090117334720700_cit25","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1111\/j.1742-4658.2011.08425.x","article-title":"Crystal\nstructure of guaiacol and phenol bound to a heme peroxidase","volume":"279","author":"Murphy","year":"2012","journal-title":"FEBS J."},{"key":"2026090117334720700_cit26","doi-asserted-by":"crossref","first-page":"9781","DOI":"10.1021\/bi801032k","article-title":"Intramolecular\nelectron transfer versus substrate oxidation in lactoperoxidase: Investigation\nof radical intermediates by stopped-flow absorption spectrophotometry\nand (9\u2013285 GHz) electron paramagnetic resonance spectroscopy","volume":"47","author":"Fielding","year":"2008","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit27","doi-asserted-by":"crossref","first-page":"16084","DOI":"10.1073\/pnas.0904535106","article-title":"Spectroscopic evidence\nfor an engineered, catalytically-active Trp radical that creates the\nunique reactivity of lignin peroxidase","volume":"106","author":"Smith","year":"2009","journal-title":"Proc.\nNatl. Acad. Sci. U.S.A."},{"key":"2026090117334720700_cit28","doi-asserted-by":"crossref","first-page":"14942","DOI":"10.1021\/bi011400h","article-title":"The role of redox-active\namino acids on Compound I stability, substrate oxidation, and protein\ncross-linking in yeast cytochrome c peroxidase","volume":"40","author":"Pfister","year":"2001","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit29","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/BF03162413","article-title":"A high-field EPR tour of radicals\nin photosystems I and II","volume":"21","author":"Un","year":"2001","journal-title":"Appl. Magn. Reson."},{"key":"2026090117334720700_cit30","doi-asserted-by":"crossref","first-page":"9356","DOI":"10.1021\/bi970886s","article-title":"EPR investigation of\nCompound I in Proteus mirabilis and bovine liver\ncatalases: Formation of porphyrin and tyrosyl radical intermediates","volume":"36","author":"Ivancich","year":"1997","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit31","doi-asserted-by":"crossref","first-page":"46082","DOI":"10.1074\/jbc.M408399200","article-title":"Influence\nof the unusual covalent adduct on the kinetics and formation of radical\nintermediates in Synechocystis catalase peroxidase:\nA stopped-flow and EPR characterization of the MET275, TYR249, and\nARG439 variants","volume":"279","author":"Jakopitsch","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2026090117334720700_cit32","doi-asserted-by":"crossref","first-page":"8857","DOI":"10.1021\/bi100499a","article-title":"Unprecedented peroxidase-like\nactivity of Rhodnius prolixus nitrophorin 2: Identification of the [FeIV\u2550O Por\u2022]+ and [FeIV\u2550O Por](Tyr38\u2022) intermediates and their\nrole(s) in substrate oxidation","volume":"49","author":"Singh","year":"2010","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit33","doi-asserted-by":"crossref","first-page":"S229","DOI":"10.1002\/mrc.1660","article-title":"The g-values\nand hyperfine coupling of amino acid radicals in proteins: Comparison\nof experimental measurements with ab initio calculations","volume":"43","author":"Un","year":"2005","journal-title":"Magn. Reson. Chem."},{"key":"2026090117334720700_cit34","doi-asserted-by":"crossref","first-page":"10713","DOI":"10.1021\/ja00148a013","article-title":"g-values\nas a probe of the local protein environment: High-field EPR of tyrosyl\nradicals in ribonucleotide reductase and photosystem-II","volume":"117","author":"Un","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"2026090117334720700_cit35","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1021\/bi802210g","article-title":"Peroxide-dependent\nformation of a covalent link between Trp51 and the heme in cytochrome c peroxidase","volume":"48","author":"Pipirou","year":"2009","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit36","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0022-2836(03)00179-7","article-title":"A novel heme and\nperoxide-dependent tryptophan-tyrosine\ncross-link in a mutant of cytochrome c peroxidase","volume":"328","author":"Bhaskar","year":"2003","journal-title":"J. Mol. Biol."},{"key":"2026090117334720700_cit37","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1021\/ja003650b","article-title":"Sensitivity\nof tyrosyl radical g-values to changes in protein structure: A high-field\nEPR study of mutants of ribonucleotide reductase","volume":"123","author":"Un","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"2026090117334720700_cit38","doi-asserted-by":"crossref","first-page":"14093","DOI":"10.1021\/ja035582+","article-title":"Protein-based\nradicals in the catalase-peroxidase of Synechocystis PCC6803: A multifrequency EPR investigation of wild-type and variants\non the environment of the heme active site","volume":"125","author":"Ivancich","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"2026090117334720700_cit39","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.jinorgbio.2006.02.009","article-title":"Identification of Trp106\nas the tryptophanyl radical intermediate in Synechocystis PCC6803 catalase-peroxidase by multifrequency electron paramagnetic\nresonance spectroscopy","volume":"100","author":"Jakopitsch","year":"2006","journal-title":"J. Inorg. Biochem."},{"key":"2026090117334720700_cit40","doi-asserted-by":"crossref","first-page":"13933","DOI":"10.1021\/bi801480r","article-title":"Engineering\nthe substrate specificity and reactivity of a heme protein: Creation\nof an ascorbate binding site in cytochrome c peroxidase","volume":"47","author":"Murphy","year":"2008","journal-title":"Biochemistry"},{"key":"2026090117334720700_cit41","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/j.2050-0416.1989.tb04624.x","article-title":"Characterization of wine yeasts for genetically modifiable\nproperties","volume":"95","author":"Thornton","year":"1992","journal-title":"J. Inst. Brew."},{"key":"2026090117334720700_cit42","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/S1389-1723(00)80040-7","article-title":"Distribution of phenolic\nyeast and\nproduction of phenolic off-flavors in wine fermentation","volume":"90","author":"Shinohara","year":"2000","journal-title":"J. Biosci. Bioeng."},{"key":"2026090117334720700_cit43","first-page":"13","article-title":"Indole\ncompounds in Saccharomyces cervisiae and Aspergilus niger","volume":"22","author":"Bau","year":"1981","journal-title":"Bot. Bull. Acad.\nSin."},{"key":"2026090117334720700_elcit129153987","doi-asserted-by":"crossref","first-page":"5743","DOI":"10.1021\/ja990562m","article-title":"Effect of\nProtein Microenvironment\non Tyrosyl Radicals. A High-Field (285 GHz) EPR, Resonance Raman,\nand Hybrid Density Functional Study","volume":"121","author":"Ivancich","year":"1999","journal-title":"J. Am.\nChem. Soc."},{"key":"2026090117334720700_elcit168907708","doi-asserted-by":"crossref","first-page":"5080","DOI":"10.1021\/ja9737127","article-title":"High-Frequency EPR and Pulsed Q-Band\nENDOR Studies\non the Origin of the Hydrogen Bond in Tyrosyl Radicals of Ribonucleotide\nReductase R2 Proteins from Mouse and Herpes Simplex Virus Type 1","volume":"120","author":"van Dam","year":"1998","journal-title":"J. Am. Chem. Soc."}],"container-title":["Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/bi500353p","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/bichaw\/article-pdf\/53\/23\/3781\/7891218\/bi500353p.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/bichaw\/article-pdf\/53\/23\/3781\/7891218\/bi500353p.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:33:56Z","timestamp":1788298436000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/bichaw\/article\/53\/23\/3781\/774305\/Identifying-the-Elusive-Sites-of-Tyrosyl-Radicals"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,5]]},"references-count":45,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2014,6,5]]},"published-print":{"date-parts":[[2014,6,17]]}},"URL":"https:\/\/doi.org\/10.1021\/bi500353p","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718436300.793507614","asserted-by":"object"}]},"ISSN":["0006-2960","1520-4995"],"issn-type":[{"value":"0006-2960","type":"print"},{"value":"1520-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6,5]]}}}