{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:41:19Z","timestamp":1769071279931,"version":"3.49.0"},"reference-count":107,"publisher":"Wiley","issue":"32","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22121001"],"award-info":[{"award-number":["22121001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["20720240124"],"award-info":[{"award-number":["20720240124"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2025,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E. coli<\/jats:italic>) repair of iron center protein (also known as YtfE) is a nonheme diiron protein that plays a pivotal role in bacterial responses to nitrosative stress, particularly in nitrite reduction and nitric oxide metabolism. Although previous studies have explored its potential as a nitrite reductase, the detailed catalytic mechanism, especially the role of its diiron center in nitrite reduction, remains poorly understood. In this study, we employed multiscale computational approaches, including quantum mechanics\/molecular mechanics (QM\/MM), quantum mechanics\/molecular mechanics metadynamics (QM\/MM MD), and quantum mechanics (QM) calculations, to elucidate the molecular mechanism of nitrite reduction by YtfE. Our findings reveal that structural reorganization of the active site, particularly the alternation of the hydrogen bonding network and coordination switch of the HONO intermediate, is critical for modulating the nitrite reduction mechanism. This work provides significant insights into the catalytic mechanism of YtfE, offering a theoretical foundation for understanding its role in bacterial stress responses and potential applications in synthetic biology and environmental remediation.<\/jats:p>","DOI":"10.1002\/chem.202500817","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T23:54:09Z","timestamp":1745884449000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["QM\/MM Unlocks The Catalytic Mechanism of YtfE: The Structural Reorganization of The Active Site Enables Nitrite\u2010to\u2010NO Conversion"],"prefix":"10.1002","volume":"31","author":[{"given":"Xitong","family":"Song","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory of Ecology\u2010Toxicological Effects &amp; Control for Emerging Contaminants College of Environmental and Biological Engineering Putian University  Putian 351100 P. R. China"},{"name":"Key Laboratory of Ecological Environment and Information Atlas Fujian Provincial University (Putian University)  Putian 351100 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3353-9411","authenticated-orcid":false,"given":"Binju","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Physical Chemistry of Solid Surfaces Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry College of Chemistry and Chemical Engineering Xiamen University  Xiamen 361005 P. R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00457"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-409547-2.14864-4"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr9500489"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr020421u"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-013118-111529"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-8545(98)00119-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-6445(03)00023-8"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7NP00061H"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar1001473"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/1074-5521(95)90222-8"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00024a031"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14160"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142443"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(96)00112-8"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja994406r"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/345593a0"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00783.x"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.6.2486"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9822714"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar030186h"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi9914199"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.c18-01001"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712073105"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja511649n"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/ic048794w"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja076121h"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja062762l"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja064837r"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi960456m"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja800654d"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0807948105"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M401268200"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419701112"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201903500"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b02545"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1020-y"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0894-z"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b06093"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/cctc.202301501"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.4c00011"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0526276"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0519607"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508473103"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja905296w"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja302072f"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315927110"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1320039111"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.9b00044"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1039\/b710047g"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-015-1329-4"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2014.09.018"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201812343"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja405047b"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9064969"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-016-1363-x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904553106"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.3c03451"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-008-0362-y"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201600990"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2006.00179.x"},{"key":"e_1_2_9_61_1","first-page":"1","volume-title":"Encyclopedia of Inorganic and Bioinorganic Chemistry","author":"Chen C. Y.","year":"2011"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c12407"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpclett.0c02200"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.670681"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.14713"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109485200"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2356"},{"key":"e_1_2_9_68_1","first-page":"1","volume-title":"Encyclopedia of Inorganic and Bioinorganic Chemistry","author":"Chen C.\u2010Y.","year":"2018"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27134051"},{"key":"e_1_2_9_70_1","volume-title":"Handbook of metalloproteins","author":"Stenkamp R. E.","year":"2006"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.1c00898"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.1c05116"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.4c02721"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202303845"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.3c00174"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202400788"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1002\/cctc.201801072"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5SC00313J"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202200257"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202402468"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200701802"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct200133y"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.5b00674"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00440"},{"key":"e_1_2_9_85_1","volume-title":"AMBER 2018","author":"Case D. A.","year":"2018"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00255"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-987X(20010415)22:5<501::AID-JCC1021>3.0.CO;2-V"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp9913012"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1163"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-2614(89)85118-8"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1080\/08927020290018769"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp9536514"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.462066"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevB.37.785"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.464913"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1039\/b508541a"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20495"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.3382344"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21759"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp9028968"},{"key":"e_1_2_9_101_1","unstructured":"The CP2K developers group. CP2K: Open Source Molecular Dynamics. Version 5.0 (Development Version r18096) Released October 24 2017. Freely available from the CP2K version history page:https:\/\/www.cp2k.org\/version_history"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpc.2004.12.014"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.2770708"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevB.54.1703"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevB.58.3641"},{"key":"e_1_2_9_106_1","volume-title":"Gaussian 09, revision D. 01","author":"Frisch M.","year":"2009"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp810292n"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.202500817","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T12:45:11Z","timestamp":1760273111000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.202500817"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":107,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2025,6,6]]}},"alternative-id":["10.1002\/chem.202500817"],"URL":"https:\/\/doi.org\/10.1002\/chem.202500817","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"assertion":[{"value":"2025-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500817"}}