{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T07:04:09Z","timestamp":1793257449106,"version":"4.5.0"},"reference-count":91,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100004358","name":"Samsung","doi-asserted-by":"publisher","award":["SSTF-BA1702-04"],"award-info":[{"award-number":["SSTF-BA1702-04"]}],"id":[{"id":"10.13039\/100004358","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2022-NR070463"],"award-info":[{"award-number":["RS-2022-NR070463"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00353098"],"award-info":[{"award-number":["RS-2024-00353098"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A5A8029490"],"award-info":[{"award-number":["2021R1A5A8029490"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1C1C1003937"],"award-info":[{"award-number":["2020R1C1C1003937"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1C1C1010943"],"award-info":[{"award-number":["2021R1C1C1010943"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-025-59645-x","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T19:03:13Z","timestamp":1747076593000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Fast product release requires active-site water dynamics in carbonic anhydrase"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2650-9879","authenticated-orcid":false,"given":"Jin Kyun","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon Woo","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3939-2457","authenticated-orcid":false,"given":"Cheol","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoyoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Woo","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob T.","family":"Andring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Lomelino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Wierman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2414-9427","authenticated-orcid":false,"given":"Aina E.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1438-3298","authenticated-orcid":false,"given":"Tae Joo","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1460-9218","authenticated-orcid":false,"given":"Cheol-Min","family":"Ghim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2792-935X","authenticated-orcid":false,"given":"Robert","family":"McKenna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6408-4317","authenticated-orcid":false,"given":"Byung Hoon","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2856-8082","authenticated-orcid":false,"given":"Duyoung","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Mo","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9350-8441","authenticated-orcid":false,"given":"Chae Un","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"59645_CR1","doi-asserted-by":"crossref","unstructured":"Frey, P. A. & Hegeman, A. D. Enzymatic reaction mechanisms. (Oxford University Press, 2007).","DOI":"10.1093\/oso\/9780195122589.001.0001"},{"key":"59645_CR2","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1146\/annurev-biochem-060409-093051","volume":"80","author":"R Wolfenden","year":"2011","unstructured":"Wolfenden, R. Benchmark reaction rates, the stability of biological molecules in water, and the evolution of catalytic power in enzymes. Annu. Rev. Biochem. 80, 645\u2013667 (2011).","journal-title":"Annu. Rev. Biochem."},{"key":"59645_CR3","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1126\/science.3051385","volume":"242","author":"J Kraut","year":"1988","unstructured":"Kraut, J. How do enzymes work? Science 242, 533\u2013540 (1988).","journal-title":"Science"},{"key":"59645_CR4","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1351\/pac200577111873","volume":"77","author":"FM Menger","year":"2005","unstructured":"Menger, F. M. An alternative view of enzyme catalysis. Pure Appl. Chem. 77, 1873\u20131886 (2005).","journal-title":"Pure Appl. Chem."},{"key":"59645_CR5","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1021\/ar040257s","volume":"38","author":"X Zhang","year":"2005","unstructured":"Zhang, X. & Houk, K. N. Why enzymes are proficient catalysts: beyond the Pauling paradigm. Acc. Chem. Res. 38, 379\u2013385 (2005).","journal-title":"Acc. Chem. Res."},{"key":"59645_CR6","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.1126\/science.1159747","volume":"320","author":"D Ringe","year":"2008","unstructured":"Ringe, D. & Petsko, G. A. Biochemistry. How enzymes work. Science 320, 1428\u20131429 (2008).","journal-title":"Science"},{"key":"59645_CR7","doi-asserted-by":"publisher","first-page":"6267","DOI":"10.1021\/bi0003689","volume":"39","author":"TC Bruice","year":"2000","unstructured":"Bruice, T. C. & Benkovic, S. J. Chemical basis for enzyme catalysis. Biochemistry 39, 6267\u20136274 (2000).","journal-title":"Biochemistry"},{"key":"59645_CR8","doi-asserted-by":"publisher","first-page":"25529","DOI":"10.1074\/jbc.273.40.25529","volume":"273","author":"WW Cleland","year":"1998","unstructured":"Cleland, W. W., Frey, P. A. & Gerlt, J. A. The low barrier hydrogen bond in enzymatic catalysis. J. Biol. Chem. 273, 25529\u201325532 (1998).","journal-title":"J. Biol. Chem."},{"key":"59645_CR9","doi-asserted-by":"publisher","first-page":"3188","DOI":"10.1021\/cr050293k","volume":"106","author":"J Gao","year":"2006","unstructured":"Gao, J. et al. Mechanisms and free energies of enzymatic reactions. Chem. Rev. 106, 3188\u20133209 (2006).","journal-title":"Chem. Rev."},{"key":"59645_CR10","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1073\/pnas.44.2.98","volume":"44","author":"D Koshland Jr","year":"1958","unstructured":"Koshland, D. Jr Application of a theory of enzyme specificity to protein synthesis. Proc. Natl Acad. Sci. USA 44, 98\u2013104 (1958).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"59645_CR11","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/nchembio.204","volume":"5","author":"ZD Nagel","year":"2009","unstructured":"Nagel, Z. D. & Klinman, J. P. A 21st century revisionist\u2019s view at a turning point in enzymology. Nat. Chem. Biol. 5, 543\u2013550 (2009).","journal-title":"Nat. Chem. Biol."},{"key":"59645_CR12","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/161707a0","volume":"161","author":"L Pauling","year":"1948","unstructured":"Pauling, L. Nature of forces between large molecules of biological interest. Nature 161, 707\u2013709 (1948).","journal-title":"Nature"},{"key":"59645_CR13","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.1021\/cr0503106","volume":"106","author":"A Warshel","year":"2006","unstructured":"Warshel, A. et al. Electrostatic basis for enzyme catalysis. Chem. Rev. 106, 3210\u20133235 (2006).","journal-title":"Chem. Rev."},{"key":"59645_CR14","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/nchembio.202","volume":"5","author":"SD Schwartz","year":"2009","unstructured":"Schwartz, S. D. & Schramm, V. L. Enzymatic transition states and dynamic motion in barrier crossing. Nat. Chem. Biol. 5, 551\u2013558 (2009).","journal-title":"Nat. Chem. Biol."},{"key":"59645_CR15","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.cbpa.2010.07.020","volume":"14","author":"VC Nashine","year":"2010","unstructured":"Nashine, V. C., Hammes-Schiffer, S. & Benkovic, S. J. Coupled motions in enzyme catalysis. Curr. Opin. Chem. Biol. 14, 644\u2013651 (2010).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"59645_CR16","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1146\/annurev-physchem-050317-014308","volume":"71","author":"CM Cheatum","year":"2020","unstructured":"Cheatum, C. M. Low-Frequency Protein Motions Coupled to Catalytic Sites. Annu. Rev. Phys. Chem. 71, 267\u2013288 (2020).","journal-title":"Annu. Rev. Phys. Chem."},{"key":"59645_CR17","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1126\/science.1085515","volume":"301","author":"SJ Benkovic","year":"2003","unstructured":"Benkovic, S. J. & Hammes-Schiffer, S. A perspective on enzyme catalysis. Science 301, 1196\u20131202 (2003).","journal-title":"Science"},{"key":"59645_CR18","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1126\/science.1198542","volume":"332","author":"G Bhabha","year":"2011","unstructured":"Bhabha, G. et al. A dynamic knockout reveals that conformational fluctuations influence the chemical step of enzyme catalysis. Science 332, 234\u2013238 (2011).","journal-title":"Science"},{"key":"59645_CR19","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/nchem.1223","volume":"4","author":"S Hay","year":"2012","unstructured":"Hay, S. & Scrutton, N. S. Good vibrations in enzyme-catalysed reactions. Nat. Chem. 4, 161\u2013168 (2012).","journal-title":"Nat. Chem."},{"key":"59645_CR20","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1038\/nature06522","volume":"450","author":"K Henzler-Wildman","year":"2007","unstructured":"Henzler-Wildman, K. & Kern, D. Dynamic personalities of proteins. Nature 450, 964\u2013972 (2007).","journal-title":"Nature"},{"key":"59645_CR21","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1002\/prot.22654","volume":"78","author":"SC Kamerlin","year":"2010","unstructured":"Kamerlin, S. C. & Warshel, A. At the dawn of the 21st century: Is dynamics the missing link for understanding enzyme catalysis? Proteins 78, 1339\u20131375 (2010).","journal-title":"Proteins"},{"key":"59645_CR22","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1021\/ar500322s","volume":"48","author":"A Kohen","year":"2015","unstructured":"Kohen, A. Role of dynamics in enzyme catalysis: substantial versus semantic controversies. Acc. Chem. Res. 48, 466\u2013473 (2015).","journal-title":"Acc. Chem. Res."},{"key":"59645_CR23","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/j.cbpa.2010.08.012","volume":"14","author":"B Ma","year":"2010","unstructured":"Ma, B. & Nussinov, R. Enzyme dynamics point to stepwise conformational selection in catalysis. Curr. Opin. Chem. Biol. 14, 652\u2013659 (2010).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"59645_CR24","doi-asserted-by":"publisher","first-page":"20897","DOI":"10.1073\/pnas.1110840108","volume":"108","author":"CU Kim","year":"2011","unstructured":"Kim, C. U., Tate, M. W. & Gruner, S. M. Protein dynamical transition at 110 K. Proc. Natl Acad. Sci. USA 108, 20897\u201320901 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"59645_CR25","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/S0301-4622(03)00096-6","volume":"105","author":"D Ringe","year":"2003","unstructured":"Ringe, D. & Petsko, G. A. The \u2018glass transition\u2019 in protein dynamics: what it is, why it occurs, and how to exploit it. Biophys. Chem. 105, 667\u2013680 (2003).","journal-title":"Biophys. Chem."},{"key":"59645_CR26","doi-asserted-by":"publisher","first-page":"5129","DOI":"10.1073\/pnas.0900336106","volume":"106","author":"H Frauenfelder","year":"2009","unstructured":"Frauenfelder, H. et al. A unified model of protein dynamics. Proc. Natl Acad. Sci. USA 106, 5129\u20135134 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"59645_CR27","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1146\/annurev.biophys.35.040405.102134","volume":"35","author":"Y Levy","year":"2006","unstructured":"Levy, Y. & Onuchic, J. N. Water mediation in protein folding and molecular recognition. Annu. Rev. Biophys. 35, 389\u2013415 (2006).","journal-title":"Annu. Rev. Biophys."},{"key":"59645_CR28","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1038\/nsmb.2120","volume":"18","author":"M Grossman","year":"2011","unstructured":"Grossman, M. et al. Correlated structural kinetics and retarded solvent dynamics at the metalloprotease active site. Nat. Struct. Mol. Biol. 18, 1102\u20131108 (2011).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"59645_CR29","unstructured":"Spiro, T. G. Zinc enzymes. (J. Wiley New York, 1983)."},{"key":"59645_CR30","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/j.1749-6632.1984.tb12310.x","volume":"429","author":"HW Davenport","year":"1984","unstructured":"Davenport, H. W. The early days of research on carbonic anhydrase. Ann. N. Y. Acad. Sci. 429, 4\u20139 (1984).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"59645_CR31","unstructured":"Chegwidden, W. R., Carter, N. D. & Edwards, Y. H. The carbonic anhydrases: new horizons. Vol. 90 (Birkh\u00e4user, 2013)."},{"key":"59645_CR32","doi-asserted-by":"crossref","unstructured":"Frost, S. C. & McKenna, R. Carbonic anhydrase: mechanism, regulation, links to disease, and industrial applications. Vol. 75 (Springer Science & Business Media, 2013).","DOI":"10.1007\/978-94-007-7359-2"},{"key":"59645_CR33","doi-asserted-by":"crossref","unstructured":"Supuran, C. T. & De Simone, G. Carbonic anhydrases as biocatalysts: from theory to medical and industrial applications. (Elsevier, 2015).","DOI":"10.1016\/B978-0-444-63258-6.00001-9"},{"key":"59645_CR34","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1113\/jphysiol.1933.sp003077","volume":"80","author":"NU Meldrum","year":"1933","unstructured":"Meldrum, N. U. & Roughton, F. J. Carbonic anhydrase. Its preparation and properties. J. Physiol. 80, 113\u2013142 (1933).","journal-title":"J. Physiol."},{"key":"59645_CR35","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1002\/qua.560360313","volume":"36","author":"JY Liang","year":"1989","unstructured":"Liang, J. Y. & Lipscomb, W. N. Theoretical-Study of Carbonic Anhydrase-Catalyzed Hydration of CO2 - a Brief Review. Int. J. Quantum Chem. 36, 299\u2013312 (1989).","journal-title":"Int. J. Quantum Chem."},{"key":"59645_CR36","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/0022-2836(92)90531-N","volume":"227","author":"K H\u00e5kansson","year":"1992","unstructured":"H\u00e5kansson, K., Carlsson, M., Svensson, L. A. & Liljas, A. Structure of native and apo carbonic anhydrase II and structure of some of its anion-ligand complexes. J. Mol. Biol. 227, 1192\u20131204 (1992).","journal-title":"J. Mol. Biol."},{"key":"59645_CR37","doi-asserted-by":"crossref","unstructured":"Lindskog, S. & Silverman, D. N. The catalytic mechanism of mammalian carbonic anhydrases. In The Carbonic Anhydrases 175\u2013195 (2000).","DOI":"10.1007\/978-3-0348-8446-4_10"},{"key":"59645_CR38","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1021\/ar7000588","volume":"40","author":"DN Silverman","year":"2007","unstructured":"Silverman, D. N. & McKenna, R. Solvent-mediated proton transfer in catalysis by carbonic anhydrase. Acc. Chem. Res. 40, 669\u2013675 (2007).","journal-title":"Acc. Chem. Res."},{"key":"59645_CR39","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1021\/cr050262p","volume":"108","author":"VM Krishnamurthy","year":"2008","unstructured":"Krishnamurthy, V. M. et al. Carbonic anhydrase as a model for biophysical and physical-organic studies of proteins and protein-ligand binding. Chem. Rev. 108, 946\u20131051 (2008).","journal-title":"Chem. Rev."},{"key":"59645_CR40","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/newbio235131a0","volume":"235","author":"A Liljas","year":"1972","unstructured":"Liljas, A. et al. Crystal structure of human carbonic anhydrase C. Nat. N. Biol. 235, 131\u2013137 (1972).","journal-title":"Nat. N. Biol."},{"key":"59645_CR41","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1002\/prot.340040406","volume":"4","author":"AE Eriksson","year":"1988","unstructured":"Eriksson, A. E., Jones, T. A. & Liljas, A. Refined structure of human carbonic anhydrase II at 2.0 \u00c5 resolution. Proteins 4, 274\u2013282 (1988).","journal-title":"Proteins"},{"key":"59645_CR42","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1021\/ar9501232","volume":"29","author":"DW Christianson","year":"1996","unstructured":"Christianson, D. W. & Fierke, C. A. Carbonic anhydrase: Evolution of the zinc binding site by nature and by design. Acc. Chem. Res. 29, 331\u2013339 (1996).","journal-title":"Acc. Chem. Res."},{"key":"59645_CR43","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1107\/S2052252517017626","volume":"5","author":"JK Kim","year":"2018","unstructured":"Kim, J. K. et al. Active-site solvent replenishment observed during human carbonic anhydrase II catalysis. IUCrJ 5, 93\u2013102 (2018).","journal-title":"IUCrJ"},{"key":"59645_CR44","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18425-5","volume":"11","author":"JK Kim","year":"2020","unstructured":"Kim, J. K. et al. Elucidating the role of metal ions in carbonic anhydrase catalysis. Nat. Commun. 11, 4557 (2020).","journal-title":"Nat. Commun."},{"key":"59645_CR45","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1021\/ar00145a005","volume":"21","author":"DN Silverman","year":"1988","unstructured":"Silverman, D. N. & Lindskog, S. The Catalytic Mechanism of Carbonic-Anhydrase - Implications of a Rate-Limiting Protolysis of Water. Acc. Chem. Res. 21, 30\u201336 (1988).","journal-title":"Acc. Chem. Res."},{"key":"59645_CR46","doi-asserted-by":"publisher","first-page":"30766","DOI":"10.1074\/jbc.M805353200","volume":"283","author":"JF Domsic","year":"2008","unstructured":"Domsic, J. F. et al. Entrapment of carbon dioxide in the active site of carbonic anhydrase II. J. Biol. Chem. 283, 30766\u201330771 (2008).","journal-title":"J. Biol. Chem."},{"key":"59645_CR47","doi-asserted-by":"publisher","first-page":"5257","DOI":"10.1073\/pnas.1520786113","volume":"113","author":"CU Kim","year":"2016","unstructured":"Kim, C. U. et al. Tracking solvent and protein movement during CO2 release in carbonic anhydrase II crystals. Proc. Natl Acad. Sci. USA 113, 5257\u20135262 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"59645_CR48","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1021\/ja01038a012","volume":"91","author":"JD Margerum","year":"1969","unstructured":"Margerum, J. D. & Petrusis, C. T. Photodecarboxylation of nitrophenylacetate ions. J. Am. Chem. Soc. 91, 2467\u20132472 (1969).","journal-title":"J. Am. Chem. Soc."},{"key":"59645_CR49","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1002\/cbic.201200659","volume":"14","author":"K Lommel","year":"2013","unstructured":"Lommel, K. et al. Caged CO2 for the direct observation of CO2-consuming reactions. ChemBioChem 14, 372\u2013380 (2013).","journal-title":"ChemBioChem"},{"key":"59645_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-021-01039-8","volume":"19","author":"Y Hirakawa","year":"2021","unstructured":"Hirakawa, Y. et al. Characterization of a novel type of carbonic anhydrase that acts without metal cofactors. BMC Biol. 19, 105 (2021).","journal-title":"BMC Biol."},{"key":"59645_CR51","doi-asserted-by":"publisher","first-page":"28124","DOI":"10.1039\/D4CP03099K","volume":"26","author":"S Yadav","year":"2024","unstructured":"Yadav, S., Kalita, S. & Dubey, K. D. Mechanism of a novel metal-free carbonic anhydrase. Phys. Chem. Chem. Phys. 26, 28124\u201328132 (2024).","journal-title":"Phys. Chem. Chem. Phys."},{"key":"59645_CR52","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/S0021-9258(18)60295-9","volume":"237","author":"S Lindskog","year":"1962","unstructured":"Lindskog, S. & Malmstr\u00f6m, B. G. Metal binding and catalytic activity in bovine carbonic anhydrase. J. Biol. Chem. 237, 1129\u20131137 (1962).","journal-title":"J. Biol. Chem."},{"key":"59645_CR53","first-page":"462","volume":"85","author":"S Lindskog","year":"1964","unstructured":"Lindskog, S. & Nyman, P. O. Metal-Binding Properties of Human Erythrocyte Carbonic Anhydrases. Biochim Biophys. Acta 85, 462\u2013474 (1964).","journal-title":"Biochim Biophys. Acta"},{"key":"59645_CR54","doi-asserted-by":"publisher","first-page":"10609","DOI":"10.1073\/pnas.0904184106","volume":"106","author":"B Sjoblom","year":"2009","unstructured":"Sjoblom, B., Polentarutti, M. & Djinovic-Carugo, K. Structural study of X-ray induced activation of carbonic anhydrase. Proc. Natl Acad. Sci. USA 106, 10609\u201310613 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"59645_CR55","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1016\/0022-2836(92)90327-G","volume":"228","author":"K Hakansson","year":"1992","unstructured":"Hakansson, K. & Wehnert, A. Structure of cobalt carbonic anhydrase complexed with bicarbonate. J. Mol. Biol. 228, 1212\u20131218 (1992).","journal-title":"J. Mol. Biol."},{"key":"59645_CR56","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1002\/prot.340150110","volume":"15","author":"Y Xue","year":"1993","unstructured":"Xue, Y. et al. Crystallographic analysis of Thr\u2010200 -> His human carbonic anhydrase II and its complex with the substrate, HCO3-. Proteins 15, 80\u201387 (1993).","journal-title":"Proteins"},{"key":"59645_CR57","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1002\/prot.340170112","volume":"17","author":"Y Xue","year":"1993","unstructured":"Xue, Y., Liljas, A., Jonsson, B. H. & Lindskog, S. Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II. Proteins 17, 93\u2013106 (1993).","journal-title":"Proteins"},{"key":"59645_CR58","doi-asserted-by":"publisher","first-page":"7628","DOI":"10.1021\/bi020053o","volume":"41","author":"S Huang","year":"2002","unstructured":"Huang, S., Sjoblom, B., Sauer-Eriksson, A. E. & Jonsson, B. H. Organization of an efficient carbonic anhydrase: implications for the mechanism based on structure-function studies of a T199P\/C206S mutant. Biochemistry 41, 7628\u20137635 (2002).","journal-title":"Biochemistry"},{"key":"59645_CR59","doi-asserted-by":"publisher","first-page":"9156","DOI":"10.1021\/bi301155z","volume":"51","author":"D West","year":"2012","unstructured":"West, D. et al. Structural and kinetic effects on changes in the CO2 binding pocket of human carbonic anhydrase II. Biochemistry 51, 9156\u20139163 (2012).","journal-title":"Biochemistry"},{"key":"59645_CR60","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1107\/S2052252520011008","volume":"7","author":"JK Kim","year":"2020","unstructured":"Kim, J. K. et al. Structural insights into the effect of active-site mutation on the catalytic mechanism of carbonic anhydrase. IUCrJ 7, 985\u2013994 (2020).","journal-title":"IUCrJ"},{"key":"59645_CR61","doi-asserted-by":"publisher","first-page":"5293","DOI":"10.1021\/bi00391a012","volume":"26","author":"JY Liang","year":"1987","unstructured":"Liang, J. Y. & Lipscomb, W. N. Hydration of carbon dioxide by carbonic anhydrase: Internal protein transfer of Zinc (2+)-bound bicarbonate. Biochemistry 26, 5293\u20135301 (1987).","journal-title":"Biochemistry"},{"key":"59645_CR62","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1107\/S2052252517018012","volume":"5","author":"A Liljas","year":"2018","unstructured":"Liljas, A. Carbonic anhydrase under pressure. IUCrJ 5, 4\u20135 (2018).","journal-title":"IUCrJ"},{"key":"59645_CR63","first-page":"393","volume":"195","author":"G Behravan","year":"1991","unstructured":"Behravan, G., Jonsson, B. H. & Lindskog, S. Fine tuning of the catalytic properties of human carbonic anhydrase II. Eff. varying Act.-site residue 200. Eur. J. Biochem. 195, 393\u2013396 (1991).","journal-title":"Eff. varying Act.-site residue 200. Eur. J. Biochem."},{"key":"59645_CR64","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.1021\/ja983930f","volume":"121","author":"VP Denisov","year":"1999","unstructured":"Denisov, V. P., Jonsson, B.-H. & Halle, B. Dynamics of Functional Water in the Active Site of Native Carbonic Anhydrase from 17O Magnetic Relaxation Dispersion. J. Am. Chem. Soc. 121, 2327\u20132328 (1999).","journal-title":"J. Am. Chem. Soc."},{"key":"59645_CR65","doi-asserted-by":"publisher","first-page":"19276","DOI":"10.1021\/jacs.9b05311","volume":"141","author":"H Singh","year":"2019","unstructured":"Singh, H. et al. Fast microsecond dynamics of the protein-water network in the active site of human carbonic anhydrase ii studied by solid-state NMR spectroscopy. J. Am. Chem. Soc. 141, 19276\u201319288 (2019).","journal-title":"J. Am. Chem. Soc."},{"key":"59645_CR66","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/357423a0","volume":"357","author":"BF Rasmussen","year":"1992","unstructured":"Rasmussen, B. F., Stock, A. M., Ringe, D. & Petsko, G. A. Crystalline ribonuclease A loses function below the dynamic transition at 220 K. Nature 357, 423\u2013424 (1992).","journal-title":"Nature"},{"key":"59645_CR67","doi-asserted-by":"publisher","first-page":"16047","DOI":"10.1073\/pnas.212637899","volume":"99","author":"PW Fenimore","year":"2002","unstructured":"Fenimore, P. W., Frauenfelder, H., McMahon, B. H. & Parak, F. G. Slaving: Solvent fluctuations dominate protein dynamics and functions. Proc. Natl Acad. Sci. USA 99, 16047\u201316051 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"59645_CR68","doi-asserted-by":"publisher","first-page":"11765","DOI":"10.1073\/pnas.1510256112","volume":"112","author":"CU Kim","year":"2015","unstructured":"Kim, C. U., Tate, M. W. & Gruner, S. M. Glass-to-cryogenic-liquid transitions in aqueous solutions suggested by crack healing. Proc. Natl Acad. Sci. USA 112, 11765\u201311770 (2015).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"59645_CR69","doi-asserted-by":"publisher","first-page":"314","DOI":"10.3891\/acta.chem.scand.42b-0314","volume":"42","author":"C Forsman","year":"1988","unstructured":"Forsman, C., Behravan, G., Osterman, A. & Jonsson, B.-H. Production of active human carbonic anhydrase ll in E. coli. Acta Chem. Scand. 42, 314\u2013318 (1988).","journal-title":"Acta Chem. Scand."},{"key":"59645_CR70","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1021\/bi00629a031","volume":"16","author":"RG Khalifah","year":"1977","unstructured":"Khalifah, R. G., Strader, D. J., Bryant, S. H. & Gibson, S. M. Carbon-13 nuclear magnetic resonance probe of active-site ionizations in human carbonic anhydrase B. Biochemistry 16, 2241\u20132247 (1977).","journal-title":"Biochemistry"},{"key":"59645_CR71","unstructured":"McPherson, A. Preparation and analysis of protein crystals. (John Wiley & Sons, 1982)."},{"key":"59645_CR72","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1021\/bi062066y","volume":"46","author":"SZ Fisher","year":"2007","unstructured":"Fisher, S. Z. et al. Atomic crystal and molecular dynamics simulation structures of human carbonic anhydrase II: Insights into the proton transfer mechanism. Biochemistry 46, 2930\u20132937 (2007).","journal-title":"Biochemistry"},{"key":"59645_CR73","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1107\/S090744490500836X","volume":"61","author":"CU Kim","year":"2005","unstructured":"Kim, C. U., Kapfer, R. & Gruner, S. M. High-pressure cooling of protein crystals without cryoprotectants. Acta Crystallogr. D. 61, 881\u2013890 (2005).","journal-title":"Acta Crystallogr. D."},{"key":"59645_CR74","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1107\/S0907444906014727","volume":"62","author":"CU Kim","year":"2006","unstructured":"Kim, C. U., Hao, Q. & Gruner, S. M. Solution of protein crystallographic structures by high-pressure cryocooling and noble-gas phasing. Acta Crystallogr. D. 62, 687\u2013694 (2006).","journal-title":"Acta Crystallogr. D."},{"key":"59645_CR75","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1098\/rspb.1990.0057","volume":"241","author":"R Henderson","year":"1990","unstructured":"Henderson, R. Cryo-protection of protein crystals against radiation damage in electron and X-ray diffraction. Proc. R. Soc. B 241, 6\u20138 (1990).","journal-title":"Proc. R. Soc. B"},{"key":"59645_CR76","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","volume":"276","author":"Z Otwinowski","year":"1997","unstructured":"Otwinowski, Z. & Minor, W. [20] Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307\u2013326 (1997).","journal-title":"Methods Enzymol."},{"key":"59645_CR77","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1107\/S0909049509003343","volume":"16","author":"AI Barker","year":"2009","unstructured":"Barker, A. I., Southworth-Davies, R. J., Paithankar, K. S., Carmichael, I. & Garman, E. F. Room-temperature scavengers for macromolecular crystallography: increased lifetimes and modified dose dependence of the intensity decay. J. Synchrotron Rad. 16, 205\u2013216 (2009).","journal-title":"J. Synchrotron Rad."},{"key":"59645_CR78","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1107\/S0907444911052085","volume":"68","author":"M Warkentin","year":"2012","unstructured":"Warkentin, M. et al. Global radiation damage at 300 and 260 K with dose rates approaching 1 MGy s\u22121. Acta Crystallogr. D. 68, 124\u2013133 (2012).","journal-title":"Acta Crystallogr. D."},{"key":"59645_CR79","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583520000128","volume":"54","author":"M Fischer","year":"2021","unstructured":"Fischer, M. Macromolecular room temperature crystallography. Q.\u00a0Rev. Biophys. 54, e1 (2021).","journal-title":"Q.\u00a0Rev. Biophys."},{"key":"59645_CR80","doi-asserted-by":"publisher","first-page":"4142","DOI":"10.1073\/pnas.1821522117","volume":"117","author":"E de la Mora","year":"2020","unstructured":"de la Mora, E. et al. Radiation damage and dose limits in serial synchrotron crystallography at cryo-and room temperatures. Proc. Natl Acad. Sci. USA 117, 4142\u20134151 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"59645_CR81","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1107\/S0907444994003112","volume":"50","author":"S Bailey","year":"1994","unstructured":"Bailey, S. The Ccp4 Suite - programs for protein crystallography. Acta Crystallogr. D. 50, 760\u2013763 (1994).","journal-title":"Acta Crystallogr. D."},{"key":"59645_CR82","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1107\/S0907444996012255","volume":"53","author":"GN Murshudov","year":"1997","unstructured":"Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D. 53, 240\u2013255 (1997).","journal-title":"Acta Crystallogr. D."},{"key":"59645_CR83","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","volume":"60","author":"P Emsley","year":"2004","unstructured":"Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D. 60, 2126\u20132132 (2004).","journal-title":"Acta Crystallogr. D."},{"key":"59645_CR84","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1107\/S0567739473000458","volume":"29","author":"LF Ten Eyck","year":"1973","unstructured":"Ten Eyck, L. F. Crystallographic fast Fourier transforms. Acta Crystallogr. A 29, 183\u2013191 (1973).","journal-title":"Acta Crystallogr. A"},{"key":"59645_CR85","unstructured":"Frisch, M. J. et al. Gaussian 16 Revision C.01 (Wallingford, CT, 2016)."},{"key":"59645_CR86","unstructured":"Dennington, R., Keith, T. & Millam, J. GaussView, version 5. (2009)."},{"key":"59645_CR87","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","volume":"14","author":"W Humphrey","year":"1996","unstructured":"Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 33\u201338 (1996).","journal-title":"J. Mol. Graph."},{"key":"59645_CR88","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1103\/PhysRevB.37.785","volume":"37","author":"CT Lee","year":"1988","unstructured":"Lee, C. T., Yang, W. T. & Parr, R. G. Development of the colle-salvetti correlation-energy formula into a functional of the electron-density. Phys. Rev. B 37, 785\u2013789 (1988).","journal-title":"Phys. Rev. B"},{"key":"59645_CR89","doi-asserted-by":"publisher","first-page":"154104","DOI":"10.1063\/1.3382344","volume":"132","author":"S Grimme","year":"2010","unstructured":"Grimme, S., Antony, J., Ehrlich, S. & Krieg, H. A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J. Chem. Phys. 132, 154104 (2010).","journal-title":"J. Chem. Phys."},{"key":"59645_CR90","doi-asserted-by":"publisher","first-page":"2561","DOI":"10.1016\/S0021-9258(18)62326-9","volume":"246","author":"RG Khalifah","year":"1971","unstructured":"Khalifah, R. G. The carbon dioxide hydration activity of carbonic anhydrase:\u00a0I. Stop-flow kinetic studies on the native human isoenzymes B and C. J. Biol. Chem. 246, 2561\u20132573 (1971).","journal-title":"J. Biol. Chem."},{"key":"59645_CR91","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/S0277-5387(00)81239-5","volume":"6","author":"RJP Williams","year":"1987","unstructured":"Williams, R. J. P. The biochemistry of zinc. Polyhedron 6, 61\u201369 (1987).","journal-title":"Polyhedron"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59645-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59645-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59645-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T20:03:16Z","timestamp":1747080196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-59645-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,12]]},"references-count":91,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["59645"],"URL":"https:\/\/doi.org\/10.1038\/s41467-025-59645-x","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,12]]},"assertion":[{"value":"17 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4404"}}