{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:54:29Z","timestamp":1776070469880,"version":"3.50.1"},"reference-count":72,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angewandte Chemie"],"published-print":{"date-parts":[[2026,4,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Mo\/W\u2010dependent formate dehydrogenases (Fdhs) catalyze the reversible reduction of CO\n                    <jats:sub>2<\/jats:sub>\n                    to formate and are key biocatalysts with high potential for CO\n                    <jats:sub>2<\/jats:sub>\n                    capture\/conversion technologies. Although previous studies have suggested the presence of two substrate\u2010access tunnels in Fdhs, experimental evidence for CO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010specific pathways has been lacking. Here, we present an integrated study of\n                    <jats:italic>Nitratidesulfovibrio vulgaris<\/jats:italic>\n                    FdhAB combining crystallography, molecular dynamics simulations, mutagenesis, and kinetic assays.\n                    <jats:italic>Nv<\/jats:italic>\n                    FdhAB crystals pressurized with Kr, O\n                    <jats:sub>2<\/jats:sub>\n                    , and CO\n                    <jats:sub>2<\/jats:sub>\n                    were used to map gas diffusion routes and uncovered a substrate\u2010retention site consistently occupied by small molecules in multiple crystal structures. Our results indicate that both substrates mostly use the main tunnel to reach this retention site, but H\n                    <jats:sub>2<\/jats:sub>\n                    O and CO\n                    <jats:sub>2<\/jats:sub>\n                    can also enter through a novel side branch before following a shared route to the buried W active site. The retention site, located at the junction of both tunnels, plays a synergistic role in enhancing CO\n                    <jats:sub>2<\/jats:sub>\n                    reduction by increasing substrate concentration near the catalytic center, thereby improving catalytic efficiency. Notably, variants affecting this site showed a selective effect for CO\n                    <jats:sub>2<\/jats:sub>\n                    reduction, with no impact on formate oxidation. These findings provide experimental evidence of a CO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010specific pathway and identify structural determinants underpinning efficient CO\n                    <jats:sub>2<\/jats:sub>\n                    reduction in this enzyme family.\n                  <\/jats:p>","DOI":"10.1002\/ange.202526133","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T06:21:22Z","timestamp":1773123682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural Insights Into CO\n                    <sub>2<\/sub>\n                    Transport Pathways in a W\u2010Formate Dehydrogenase: Structural Basis for CO\n                    <sub>2<\/sub>\n                    Reduction"],"prefix":"10.1002","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0003-9637","authenticated-orcid":false,"given":"Guilherme","family":"Vilela\u2010Alves","sequence":"first","affiliation":[{"name":"UCIBIO Applied Molecular Biosciences Unit and Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy Department of Chemistry NOVA School of Science and Technology Universidade NOVA de Lisboa  Caparica Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-2053","authenticated-orcid":false,"given":"Rita Rebelo","family":"Manuel","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Oeiras Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6042-7151","authenticated-orcid":false,"given":"Guilherme","family":"Martins","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Oeiras Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1268-7826","authenticated-orcid":false,"given":"Philippe","family":"Carpentier","sequence":"additional","affiliation":[{"name":"European Synchrotron Radiation Facility  Grenoble France"},{"name":"Institut de Recherche Interdisciplinaire de Grenoble (IRIG) Laboratoire Chimie et Biologie des M\u00e9taux (LCBM) Universit\u00e9 Grenoble Alpes, CNRS, CEA  Grenoble France"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-3669","authenticated-orcid":false,"given":"Agata","family":"Raczy\u0144ska","sequence":"additional","affiliation":[{"name":"Tunneling Group Biotechnology Centre Silesian University of Technology  Gliwice Poland"},{"name":"Department of Bioinformatics and Artificial Intelligence Applications Polish\u2010Japanese Academy of Information Technology  Warsaw Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7650-9263","authenticated-orcid":false,"given":"Maciej","family":"Szaleniec","sequence":"additional","affiliation":[{"name":"Jerzy Haber Institute of Catalysis and Surface Chemistry Polish Academy of Sciences  Krakow Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3283-4520","authenticated-orcid":false,"given":"In\u00eas A. Cardoso","family":"Pereira","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Oeiras Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"UCIBIO Applied Molecular Biosciences Unit and Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy Department of Chemistry NOVA School of Science and Technology Universidade NOVA de Lisboa  Caparica Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-0420","authenticated-orcid":false,"given":"Cristiano","family":"Mota","sequence":"additional","affiliation":[{"name":"UCIBIO Applied Molecular Biosciences Unit and Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy Department of Chemistry NOVA School of Science and Technology Universidade NOVA de Lisboa  Caparica Portugal"}]}],"member":"311","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.4209\/aaqr.2013.10.0326"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcou.2013.08.001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr300463y"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2021.07.011"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.0c00086"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.1c00914"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3498"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2022.111903"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13068-018-1236-3"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.organomet.9b00809"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1810386115"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201814419"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsenergylett.9b02436"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-006-0129-2"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ic502880y"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.688457"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-011-0813-8"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/ic3028034"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-018-1608-y"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.2c00151"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf9284"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-023-01484-2"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010476"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4SC02394C"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600576716010992"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600576714000855"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798323010707"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600576722007580"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CC04557H"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2017.10.014"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-020-01814-y"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1712267115"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002708"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz946"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.5c02382"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2052252523006437"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04971-z"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15614-0"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202405120"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.1c00058"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0909049506004341"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600577518007166"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600577520004002"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1107\/S1600577522002818"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444913000061"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444911007773"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1107\/S010876731809640X"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889807021206"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910045749"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444910007493"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904023510"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889809008784"},{"key":"e_1_2_7_55_1","unstructured":"Schrodinger LLC 2019."},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2019.06.007"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae241"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b03941"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1033.2003.03619.x"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244758"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja508647u"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcou.2024.102754"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.785576"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2017.04.027"},{"key":"e_1_2_7_65_1","unstructured":"M. J.Frisch G. W.Trucks H. B.Schlegel et\u00a0al. (2016) Gaussian 16 Rev. C.01 Wallingford."},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1121"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.5b00390"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00051a040"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.2c01104"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki464"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21224"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.3c01153"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct300418h"}],"container-title":["Angewandte Chemie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ange.202526133","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ange.202526133","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ange.202526133","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:02:08Z","timestamp":1776067328000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ange.202526133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":72,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,4,13]]}},"alternative-id":["10.1002\/ange.202526133"],"URL":"https:\/\/doi.org\/10.1002\/ange.202526133","archive":["Portico"],"relation":{},"ISSN":["0044-8249","1521-3757"],"issn-type":[{"value":"0044-8249","type":"print"},{"value":"1521-3757","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]},"assertion":[{"value":"2025-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e26133"}}