{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T20:16:34Z","timestamp":1788466594152,"version":"build-2803163510"},"reference-count":35,"publisher":"American Chemical Society (ACS)","issue":"35","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP23H04879"],"award-info":[{"award-number":["JP23H04879"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JP26K03064"],"award-info":[{"award-number":["JP26K03064"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["JPMXP1323015474"],"award-info":[{"award-number":["JPMXP1323015474"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fluoroacetate dehalogenase (FAcD) is a unique, nonmetal-dependent enzyme capable of cleaving the inert C\u2013F bond of fluoroacetate (FA) under mild conditions, making it an important enzymatic model for organofluorine degradation. This study investigated the catalytic degradation mechanism of FA by FAcD using density functional theory calculations with an active-site cluster model. The model included the FA substrate, two crystallographic water molecules, and the key amino acid residues surrounding the active site. An integrated energy profile connecting defluorination and hydrolysis was obtained within a single computational framework. The calculated reaction pathway consists of four elementary steps: (I) C\u2013F bond activation, (II) nucleophilic attack, (III) C\u2013O bond cleavage, and (IV) proton transfer. Structural analyses showed that Arg111, Arg114, and Tyr219 stabilize the carboxylate group of FA and His155, Trp156, and Tyr219 stabilize the fluoride anion during C\u2013F bond cleavage. Furthermore, His155 was suggested to activate the hydrolytic water molecule and participate directly in the nucleophilic attack step. These findings provide a unified quantum-chemical description of FAcD-catalyzed defluorination and hydrolysis and offer insights into the design of engineered enzymes and biomimetic catalysts for organofluorine degradation.<\/jats:p>","DOI":"10.1021\/acs.jpcb.6c03397","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:33:43Z","timestamp":1785854023000},"page":"8805-8814","source":"Crossref","is-referenced-by-count":0,"title":["Revisiting the\nMechanism of Fluoroacetate Dehalogenase-Catalyzed\nDegradation of Fluorocarboxylic Acid via Cluster Models"],"prefix":"10.1021","volume":"130","author":[{"given":"Manussada","family":"Ratanasak","sequence":"first","affiliation":[{"name":"University of Tsukuba , , 1-1-1 Tennodai, Tsukuba , ,","place":["Ibaraki, Japan, 305-8577"]},{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-1996","authenticated-orcid":true,"given":"Yuta","family":"Hori","sequence":"additional","affiliation":[{"name":"University of Tsukuba , , 1-1-1 Tennodai, Tsukuba , ,","place":["Ibaraki, Japan, 305-8577"]},{"name":"Kanazawa University , , Kakuma-machi , , ,","place":["Kanazawa, Ishikawa, Japan, 920-1192"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6877-9223","authenticated-orcid":true,"given":"Kohei","family":"Sato","sequence":"additional","affiliation":[{"name":"Shizuoka University , , , ,","place":["Hamamatsu, Shizuoka, Japan, 432-8561"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanyada","family":"Rungrotmongkol","sequence":"additional","affiliation":[{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-6007","authenticated-orcid":true,"given":"Yasuteru","family":"Shigeta","sequence":"additional","affiliation":[{"name":"University of Tsukuba , , 1-1-1 Tennodai, Tsukuba , ,","place":["Ibaraki, Japan, 305-8577"]},{"name":"Chulalongkorn University , , ,","place":["Bangkok, Thailand, 10330"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"issue":"9","key":"2026090315292770800_cit1","doi-asserted-by":"publisher","first-page":"101467","DOI":"10.1016\/j.isci.2020.101467","article-title":"Current Contributions\nof Organofluorine Compounds to the Agrochemical Industry","volume":"23","author":"Ogawa","year":"2020","journal-title":"iScience"},{"issue":"7","key":"2026090315292770800_cit2","doi-asserted-by":"publisher","first-page":"3065","DOI":"10.1002\/ps.7921","article-title":"Recent developments\nin fluorine-containing pesticides","volume":"80","author":"Jeschke","year":"2024","journal-title":"Pest Manag.\nSci."},{"issue":"19","key":"2026090315292770800_cit3","doi-asserted-by":"publisher","first-page":"2790","DOI":"10.3390\/polym16192790","article-title":"Water Repellent Coating in Textile,\nPaper and Bioplastic Polymers: A Comprehensive Review","volume":"16","author":"Rungruangkitkrai","year":"2024","journal-title":"Polymers"},{"issue":"2","key":"2026090315292770800_cit4","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1039\/B711844A","article-title":"Understanding\norganofluorine chemistry. An introduction to the C\u2013F bond","volume":"37","author":"O\u2019Hagan","year":"2008","journal-title":"Chem. Soc. Rev."},{"issue":"2","key":"2026090315292770800_cit5","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1002\/jat.1118","article-title":"Toxicology of fluoroacetate: a review,\nwith possible directions for therapy research","volume":"26","author":"Goncharov","year":"2006","journal-title":"J. Appl. Toxicol."},{"issue":"19","key":"2026090315292770800_cit6","doi-asserted-by":"publisher","first-page":"7461","DOI":"10.1021\/ja200277d","article-title":"Mapping the Reaction\nCoordinates of Enzymatic Defluorination","volume":"133","author":"Chan","year":"2011","journal-title":"J.\nAm. Chem. Soc."},{"issue":"20","key":"2026090315292770800_cit7","doi-asserted-by":"publisher","first-page":"4966","DOI":"10.1111\/febs.16903","article-title":"Structural insights\ninto hydrolytic defluorination of difluoroacetate by microbial fluoroacetate\ndehalogenases","volume":"290","author":"Khusnutdinova","year":"2023","journal-title":"FEBS J."},{"issue":"47","key":"2026090315292770800_cit8","doi-asserted-by":"publisher","first-page":"30897","DOI":"10.1074\/jbc.273.47.30897","article-title":"Reaction Mechanism\nof Fluoroacetate Dehalogenase from Moraxella sp. B","volume":"273","author":"Liu","year":"1998","journal-title":"J. Biol. Chem."},{"issue":"8","key":"2026090315292770800_cit9","doi-asserted-by":"publisher","first-page":"3434","DOI":"10.1016\/S0021-9258(18)97236-4","article-title":"The Enzymatic\nCleavage of the Carbon-Fluorine Bond in Fluoroacetate","volume":"240","author":"Goldman","year":"1965","journal-title":"J. Biol. Chem."},{"issue":"8","key":"2026090315292770800_cit10","doi-asserted-by":"publisher","first-page":"2630","DOI":"10.1128\/JB.01654-08","article-title":"X-Ray crystallographic\nand mutational\nstudies of fluoroacetate dehalogenase from Burkholderia sp. strain\nFA1","volume":"191","author":"Jitsumori","year":"2009","journal-title":"J. Bacteriol."},{"issue":"30","key":"2026090315292770800_cit11","doi-asserted-by":"publisher","first-page":"7394","DOI":"10.1002\/chem.200801813","article-title":"The Catalytic\nMechanism of Fluoroacetate Dehalogenase: A Computational Exploration\nof Biological Dehalogenation","volume":"15","author":"Kamachi","year":"2009","journal-title":"Chem.\u2013Eur.\nJ."},{"issue":"8","key":"2026090315292770800_cit12","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.3390\/ijms17081372","article-title":"How Many Conformations\nof Enzymes Should Be Sampled for DFT\/MM Calculations? A Case Study\nof Fluoroacetate Dehalogenase","volume":"17","author":"Li","year":"2016","journal-title":"Int. J. Mol.\nSci."},{"key":"2026090315292770800_cit13","doi-asserted-by":"publisher","first-page":"126803","DOI":"10.1016\/j.chemosphere.2020.126803","article-title":"Fluoroacetate dehalogenase\ncatalyzed dehalogenation of halogenated\ncarboxylic acids: A QM\/MM approach","volume":"254","author":"Yue","year":"2020","journal-title":"Chemosphere"},{"key":"2026090315292770800_cit14","doi-asserted-by":"publisher","first-page":"113399","DOI":"10.1016\/j.comptc.2021.113399","article-title":"Influence of the quantum\nmechanical region size in QM\/MM modelling:\nA case study of fluoroacetate dehalogenase catalyzed CF bond cleavage","volume":"1204","author":"Kang","year":"2021","journal-title":"Comput. Theor. 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Educ."},{"issue":"2","key":"2026090315292770800_cit32","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1021\/ar1000956","article-title":"How to Conceptualize\nCatalytic Cycles? The Energetic Span Model","volume":"44","author":"Kozuch","year":"2011","journal-title":"Acc. Chem. Res."},{"issue":"5","key":"2026090315292770800_cit33","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1002\/jcc.21669","article-title":"Automatic analysis of computed catalytic\ncycles","volume":"32","author":"Uhe","year":"2011","journal-title":"J. Comput. Chem."},{"key":"2026090315292770800_cit34","doi-asserted-by":"publisher","first-page":"104999","DOI":"10.1016\/j.envint.2019.104999","article-title":"Harnessing fluoroacetate\ndehalogenase for defluorination of fluorocarboxylic acids: in silico\nand in vitro approach","volume":"131","author":"Li","year":"2019","journal-title":"Environ. Int."},{"issue":"2","key":"2026090315292770800_cit35","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1021\/ma50003a019","article-title":"Method for estimating the configurational\nentropy of\nmacromolecules","volume":"14","author":"Karplus","year":"1981","journal-title":"Macromolecules"}],"container-title":["The Journal of Physical\nChemistry B"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jpcb.6c03397","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/35\/8805\/66362055\/acs.jpcb.6c03397.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article-pdf\/130\/35\/8805\/66362055\/acs.jpcb.6c03397.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:29:32Z","timestamp":1788463772000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jpcbfk\/article\/130\/35\/8805\/5238710\/Revisiting-the-Mechanism-of-Fluoroacetate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":35,"journal-issue":{"issue":"35","published-online":{"date-parts":[[2026,8,3]]},"published-print":{"date-parts":[[2026,9,3]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jpcb.6c03397","relation":{},"ISSN":["1520-6106","1520-5207"],"issn-type":[{"value":"1520-6106","type":"print"},{"value":"1520-5207","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}