{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T12:34:17Z","timestamp":1786365257289,"version":"build-2736575974"},"reference-count":68,"publisher":"American Chemical Society (ACS)","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000165","name":"Division of Chemistry","doi-asserted-by":"publisher","award":["CHE-2203616"],"award-info":[{"award-number":["CHE-2203616"]}],"id":[{"id":"10.13039\/100000165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000165","name":"Division of Chemistry","doi-asserted-by":"publisher","award":["CHE-2203628"],"award-info":[{"award-number":["CHE-2203628"]}],"id":[{"id":"10.13039\/100000165","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013316","name":"Strategic Environmental Research and Development Program","doi-asserted-by":"publisher","award":["ER23-3830"],"award-info":[{"award-number":["ER23-3830"]}],"id":[{"id":"10.13039\/100013316","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000146","name":"Division of Chemical, Bioengineering, Environmental, and Transport Systems","doi-asserted-by":"crossref","award":["1846945"],"award-info":[{"award-number":["1846945"]}],"id":[{"id":"10.13039\/100000146","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>1,4-Dioxane is a widespread groundwater contaminant frequently co-occurring with chlorinated solvents. The group-6 propane monooxygenase (PRM) from Mycobacterium dioxanotrophicus PH-06 degrades dioxane efficiently, yet the molecular determinants underlying its broad substrate spectrum and inhibition behavior remain unresolved. Here, we combined AlphaFold2-based structure prediction, molecular docking, and alchemical free energy calculations to systematically characterize ligand binding in PH-06 PRM. The catalytic center (residues 87\u2013265), coordinated by two histidines and four glutamates, exhibited calculated binding free energies for five substrates (C2\u2013C4 alkanes and cyclic ethers) that significantly correlated with experimentally determined degradation rates (p &amp;lt; 0.05), supporting the ability of ligand binding thermodynamics to capture major substrate-recognition trends in PH-06 PRM. In addition, we identified a remote binding site (residues 329\u2013446) approximately 30 \u00c5 from the catalytic center. Thermodynamic analysis indicates that this remote site can attract methane and ethane, potentially limiting their access to the catalytic center. Comparative binding analyses of three common chlorinated solvent inhibitors (i.e., trichloroethylene [TCE], 1,1-dichloroethylene [DCE], and 1,1,1-trichloroethane [TCA]) revealed distinct site preferences consistent with their experimentally observed inhibition modes. Noncompetitive inhibitors (DCE and TCA) displayed stronger affinity for the remote site, whereas the competitive inhibitor TCE exhibited comparable affinity for both binding regions. Sequence conservation, contact probability analysis, and Gene Ontology enrichment further suggest the structural relevance of the remote site and its possible role in ligand recognition and inhibitor selectivity. These findings demonstrate that the AlphaFold-guided free energy calculations can capture experimentally observed substrate and inhibitor trends in PH-06 PRM, while identifying a remote ligand-binding pocket that warrants further mechanistic investigation.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c01081","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:10:02Z","timestamp":1785849002000},"page":"9344-9352","source":"Crossref","is-referenced-by-count":0,"title":["Computational Characterization of Ligand Recognition\nand Inhibition in a 1,4-Dioxane-Degrading Propane Monooxygenase"],"prefix":"10.1021","volume":"66","author":[{"given":"Yishai","family":"Gilron","sequence":"first","affiliation":[{"name":"Arizona State University , , , ,","place":["Mesa, Arizona, United States, 85212"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5825-564X","authenticated-orcid":true,"given":"Jose Manual Diaz","family":"Antunes","sequence":"additional","affiliation":[{"name":"New Jersey Institute of Technology , , , ,","place":["Newark, New Jersey, United States, 07102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devi Kumari","family":"Dhakal Gaudel","sequence":"additional","affiliation":[{"name":"New Jersey Institute of Technology , , , ,","place":["Newark, New Jersey, United States, 07102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7664-4836","authenticated-orcid":true,"given":"Mengyan","family":"Li","sequence":"additional","affiliation":[{"name":"New Jersey Institute of Technology , , , ,","place":["Newark, New Jersey, United States, 07102"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9603-009X","authenticated-orcid":true,"given":"Wenwei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Arizona State University , , , ,","place":["Mesa, Arizona, United States, 85212"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"4","key":"2026081008095729600_cit1","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/S0168-6445(03)00023-8","article-title":"Evolution of the Soluble Diiron Monooxygenases","volume":"27","author":"Leahy","year":"2003","journal-title":"FEMS Microbiol. Rev."},{"key":"2026081008095729600_cit2","doi-asserted-by":"publisher","first-page":"106527","DOI":"10.1016\/j.ympev.2019.106527","article-title":"Beneath the Surface: Evolution of\nMethane Activity\nin the Bacterial Multicomponent Monooxygenases","volume":"139","author":"Osborne","year":"2019","journal-title":"Mol. Phylogenet. Evol."},{"issue":"2","key":"2026081008095729600_cit3","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.70050","article-title":"Phylogenetic\nand Functional Diversity\nof Soluble Di-Iron Monooxygenases","volume":"27","author":"Yang","year":"2025","journal-title":"Environ.\nMicrobiol."},{"issue":"1","key":"2026081008095729600_cit4","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1146\/annurev-biochem-013118-111529","article-title":"Soluble\nMethane Monooxygenase","volume":"88","author":"Banerjee","year":"2019","journal-title":"Annu. Rev. Biochem."},{"key":"2026081008095729600_cit5","volume-title":"1,4-Dioxane Biodegradation\nin Propanotrophs: Molecular Foundations and Implications for Environmental\nRemediation","author":"Li","year":"2020"},{"issue":"7","key":"2026081008095729600_cit6","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1111\/j.1462-2920.2006.01015.x","article-title":"Soluble Di-Iron Monooxygenase Gene\nDiversity in Soils, Sediments and Ethene Enrichments","volume":"8","author":"Coleman","year":"2006","journal-title":"Environ. Microbiol."},{"issue":"2","key":"2026081008095729600_cit7","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.16567","article-title":"A Novel Soluble\nDi-iron Monooxygenase from the Soil Bacterium Solimonas Soli","volume":"26","author":"Yang","year":"2024","journal-title":"Environ. Microbiol."},{"issue":"4","key":"2026081008095729600_cit8","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1021\/ar1001473","article-title":"Dioxygen Activation in Soluble Methane Monooxygenase","volume":"44","author":"Tinberg","year":"2011","journal-title":"Acc. Chem. Res."},{"key":"2026081008095729600_cit9","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/bs.mie.2017.07.016","article-title":"Use of Isotopes and Isotope Effects\nfor Investigations of Diiron Oxygenase Mechanisms","volume":"596","author":"Banerjee","year":"2017","journal-title":"Methods Enzymol."},{"issue":"17","key":"2026081008095729600_cit10","doi-asserted-by":"publisher","first-page":"10023","DOI":"10.1016\/S0021-9258(18)81762-8","article-title":"Methane Monooxygenase\nfrom Methylosinus Trichosporium OB3b","volume":"264","author":"Fox","year":"1989","journal-title":"J. Biol.\nChem."},{"issue":"6","key":"2026081008095729600_cit11","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1021\/cr950244f","article-title":"Mechanistic Studies\non the Hydroxylation of Methane by Methane Monooxygenase","volume":"103","author":"Baik","year":"2003","journal-title":"Chem. Rev."},{"key":"2026081008095729600_cit12","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/0076-6879(90)88032-6","article-title":"[30] Soluble Methane Monooxygenase from Methylococcus\nCapsulatus Bath","volume":"188","author":"Pilkington","year":"1990","journal-title":"Methods Enzymol."},{"issue":"3","key":"2026081008095729600_cit13","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1021\/acs.est.9b05671","article-title":"Distinct Catalytic\nBehaviors between\nTwo 1,4-Dioxane-Degrading Monooxygenases: Kinetics, Inhibition, and\nSubstrate Range","volume":"54","author":"Li","year":"2020","journal-title":"Environ. Sci. Technol."},{"issue":"2","key":"2026081008095729600_cit14","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1021\/acs.estlett.7b00504","article-title":"A Novel Propane\nMonooxygenase Initiating Degradation\nof 1,4-Dioxane by Mycobacterium Dioxanotrophicus PH-06","volume":"5","author":"Deng","year":"2018","journal-title":"Environ. Sci. Technol. Lett."},{"issue":"1","key":"2026081008095729600_cit15","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1021\/ez400176h","article-title":"The Abundance\nof Tetrahydrofuran\/Dioxane Monooxygenase Genes (thmA\/dxmA) and 1,4-Dioxane\nDegradation Activity Are Significantly Correlated at Various Impacted\nAquifers","volume":"1","author":"Li","year":"2014","journal-title":"Environ. Sci. Technol. Lett."},{"issue":"12","key":"2026081008095729600_cit16","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1021\/acs.estlett.5c00963","article-title":"Cluster-Specific Biomarkers for Effective\nAssessment of 1,4-Dioxane Biodegradation Potentials for Natural Attenuation\nand Propane Biosparging","volume":"12","author":"Antunes","year":"2025","journal-title":"Environ. Sci. Technol.\nLett."},{"key":"2026081008095729600_cit17","volume-title":"Environmental Investigation\nand Remediation: 1,4-Dioxane and Other Solvent Stabilizers","author":"Mohr","year":"2020","edition":"2"},{"issue":"2","key":"2026081008095729600_cit18","doi-asserted-by":"publisher","DOI":"10.1002\/rem.70060","article-title":"Evaluation of 1,4-Dioxane Natural Attenuation After In Situ Propane\nBiosparging: Bench-Scale Microcosm Tests and Field Metadata Analysis","volume":"36","author":"Antunes","year":"2026","journal-title":"Remediat. J."},{"key":"2026081008095729600_cit19","unstructured":"Frank, R.\n          \n          Lautenberg Chemical Safety\nfor the 21st Century Act, Public Law, 2016;\npp 114\u2013182."},{"issue":"7873","key":"2026081008095729600_cit20","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly Accurate Protein\nStructure Prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"issue":"8","key":"2026081008095729600_cit21","doi-asserted-by":"publisher","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0:\nNew Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"issue":"2","key":"2026081008095729600_cit22","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed\nand Accuracy of\nDocking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"issue":"16","key":"2026081008095729600_cit23","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated\nDocking with Selective Receptor Flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"issue":"5","key":"2026081008095729600_cit24","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA Methods to Estimate Ligand-Binding Affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin. Drug Discovery"},{"issue":"11","key":"2026081008095729600_cit25","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1080\/17460441.2021.1942836","article-title":"What Is the\nCurrent Value of MM\/PBSA and MM\/GBSA Methods in Drug Discovery?","volume":"16","author":"Tuccinardi","year":"2021","journal-title":"Expert Opin. Drug Discovery"},{"issue":"6","key":"2026081008095729600_cit26","doi-asserted-by":"publisher","first-page":"2844","DOI":"10.1021\/acs.jcim.1c00091","article-title":"VAD-MM\/GBSA:\nA Variable Atomic Dielectric MM\/GBSA Model for Improved Accuracy in\nProtein\u2013Ligand Binding Free Energy Calculations","volume":"61","author":"Wang","year":"2021","journal-title":"J. Chem. Inf. Model."},{"issue":"16","key":"2026081008095729600_cit27","doi-asserted-by":"publisher","first-page":"9478","DOI":"10.1021\/acs.chemrev.9b00055","article-title":"End-Point Binding Free Energy Calculation\nwith MM\/PBSA\nand MM\/GBSA: Strategies and Applications in Drug Design","volume":"119","author":"Wang","year":"2019","journal-title":"Chem. Rev."},{"issue":"1","key":"2026081008095729600_cit28","doi-asserted-by":"publisher","first-page":"18378","DOI":"10.33011\/livecoms.2.1.18378","article-title":"Best Practices for Alchemical Free\nEnergy Calculations [Article v1.0]","volume":"2","author":"Mey","year":"2020","journal-title":"Living J.\nComput. Mol. Sci."},{"issue":"19","key":"2026081008095729600_cit29","doi-asserted-by":"publisher","first-page":"7214","DOI":"10.1021\/acs.jcim.4c01024","article-title":"Alchemical Transformations and Beyond:\nRecent Advances and Real-World Applications of Free Energy Calculations\nin Drug Discovery","volume":"64","author":"Qian","year":"2024","journal-title":"J. Chem. Inf. Model."},{"issue":"4","key":"2026081008095729600_cit30","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1007\/s10532-008-9240-0","article-title":"Biodegradation\nof 1,4-Dioxane and Transformation of Related Cyclic Compounds by a\nNewly Isolated Mycobacterium Sp. PH-06","volume":"20","author":"Kim","year":"2009","journal-title":"Biodegradation"},{"key":"2026081008095729600_cit31","doi-asserted-by":"publisher","first-page":"D570","DOI":"10.1093\/nar\/gkz1035","article-title":"MGnify:\nThe Microbiome Analysis Resource\nin 2020","volume":"48","author":"Mitchell","year":"2020","journal-title":"Nucleic Acids Res."},{"issue":"6","key":"2026081008095729600_cit32","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1093\/bioinformatics\/btu739","article-title":"UniRef\nClusters: A Comprehensive and Scalable Alternative for Improving Sequence\nSimilarity Searches","volume":"31","author":"Suzek","year":"2015","journal-title":"Bioinformatics"},{"issue":"7","key":"2026081008095729600_cit33","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/s41592-019-0437-4","article-title":"Protein-Level\nAssembly Increases\nProtein Sequence Recovery from Metagenomic Samples Manyfold","volume":"16","author":"Steinegger","year":"2019","journal-title":"Nat. Methods"},{"issue":"6","key":"2026081008095729600_cit34","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making Protein Folding\nAccessible to All","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"issue":"11","key":"2026081008095729600_cit35","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4792","article-title":"UCSF ChimeraX:\nTools for Structure\nBuilding and Analysis","volume":"32","author":"Meng","year":"2023","journal-title":"Protein Sci."},{"issue":"5","key":"2026081008095729600_cit36","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1021\/ja003240n","article-title":"Crystal Structures of the Soluble Methane Monooxygenase\nHydroxylase from Methylococcus Capsulatus (Bath) Demonstrating Geometrical\nVariability at the Dinuclear Iron Active Site","volume":"123","author":"Whittington","year":"2001","journal-title":"J. Am. Chem. Soc."},{"issue":"1","key":"2026081008095729600_cit37","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1146\/annurev.arplant.54.031902.134915","article-title":"Membrane-Bound Diiron Carboxylate Proteins","volume":"54","author":"Berthold","year":"2003","journal-title":"Annu. Rev. Plant Biol."},{"issue":"6","key":"2026081008095729600_cit38","doi-asserted-by":"publisher","first-page":"2733","DOI":"10.1021\/ct400146w","article-title":"Rational Design\nof Particle Mesh Ewald Compatible Lennard-Jones Parameters for + 2\nMetal Cations in Explicit Solvent","volume":"9","author":"Li","year":"2013","journal-title":"J. Chem.\nTheory Comput."},{"issue":"7","key":"2026081008095729600_cit39","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1093\/bioinformatics\/btt055","article-title":"GROMACS 4.5: A High-Throughput\nand Highly Parallel Open Source Molecular Simulation Toolkit","volume":"29","author":"Pronk","year":"2013","journal-title":"Bioinformatics"},{"issue":"8","key":"2026081008095729600_cit40","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1002\/prot.22711","article-title":"Improved Side-chain\nTorsion Potentials for the Amber ff99SB Protein Force Field","volume":"78","author":"Lindorff-Larsen","year":"2010","journal-title":"Proteins Struct. Funct. Bioinforma."},{"issue":"9","key":"2026081008095729600_cit41","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development\nand Testing of a General Amber Force Field","volume":"25","author":"Wang","year":"2004","journal-title":"J. Comput. Chem."},{"issue":"2","key":"2026081008095729600_cit42","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","article-title":"Automatic Atom Type\nand Bond Type Perception in Molecular Mechanical Calculations","volume":"25","author":"Wang","year":"2006","journal-title":"J. Mol. Graph. Model."},{"issue":"2","key":"2026081008095729600_cit43","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison\nof Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"issue":"6","key":"2026081008095729600_cit44","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/0009-2614(94)00397-1","article-title":"Avoiding\nSingularities and Numerical Instabilities in Free Energy Calculations\nBased on Molecular Simulations","volume":"222","author":"Beutler","year":"1994","journal-title":"Chem. Phys.\nLett."},{"issue":"1","key":"2026081008095729600_cit45","doi-asserted-by":"publisher","first-page":"014101","DOI":"10.1063\/1.2408420","article-title":"Canonical\nSampling through Velocity\nRescaling","volume":"126","author":"Bussi","year":"2007","journal-title":"J. Chem. Phys."},{"issue":"8","key":"2026081008095729600_cit46","doi-asserted-by":"publisher","first-page":"3684","DOI":"10.1063\/1.448118","article-title":"Molecular\nDynamics with Coupling to an External Bath","volume":"81","author":"Berendsen","year":"1984","journal-title":"J. Chem. Phys."},{"issue":"11","key":"2026081008095729600_cit47","doi-asserted-by":"publisher","first-page":"114107","DOI":"10.1063\/5.0020514","article-title":"Pressure Control Using Stochastic Cell Rescaling","volume":"153","author":"Bernetti","year":"2020","journal-title":"J. Chem. Phys."},{"key":"2026081008095729600_cit48","doi-asserted-by":"publisher","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle Mesh\nEwald: An N\u00b7log\n(N) Method for Ewald Sums in Large Systems","volume":"98","author":"Darden","year":"1993","journal-title":"J. Chem. Phys."},{"key":"2026081008095729600_cit49","first-page":"98","volume-title":"A Python Package for the Rapid Analysis\nof Molecular Dynamics Simulations","author":"Gowers","year":"2016"},{"issue":"16","key":"2026081008095729600_cit50","doi-asserted-by":"publisher","first-page":"5814","DOI":"10.1021\/ja044099b","article-title":"Product Bound Structures of the Soluble Methane Monooxygenase\nHydroxylase from Methylococcus Capsulatus (Bath): Protein Motion in\nthe \u03b1-Subunit","volume":"127","author":"Sazinsky","year":"2005","journal-title":"J. Am. Chem. Soc."},{"issue":"32","key":"2026081008095729600_cit51","doi-asserted-by":"publisher","first-page":"2946","DOI":"10.1021\/acs.biochem.0c00459","article-title":"Structural\nStudies of the Methylosinus Trichosporium OB3b Soluble Methane Monooxygenase\nHydroxylase and Regulatory Component Complex Reveal a Transient Substrate\nTunnel","volume":"59","author":"Jones","year":"2020","journal-title":"Biochemistry"},{"issue":"3","key":"2026081008095729600_cit52","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1021\/acs.chemrev.3c00727","article-title":"Direct\nMethane Oxidation by Copper- and Iron-Dependent\nMethane Monooxygenases","volume":"124","author":"Tucci","year":"2024","journal-title":"Chem. Rev."},{"issue":"7437","key":"2026081008095729600_cit53","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature11880","article-title":"Control of Substrate\nAccess to the Active Site in Methane Monooxygenase","volume":"494","author":"Lee","year":"2013","journal-title":"Nature"},{"issue":"2","key":"2026081008095729600_cit54","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1002\/(sici)1097-0134(199710)29:2&lt;141::aid-prot2&gt;3.0.co;2-g","article-title":"Crystal Structures of the Methane Monooxygenase Hydroxylase\nfromMethylococcus Capsulatus (Bath): Implications for Substrate Gating\nand Component Interactions","volume":"29","author":"Rosenzweig","year":"1997","journal-title":"Proteins Struct.\nFunct. Genet."},{"issue":"8","key":"2026081008095729600_cit55","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1021\/ar030204v","article-title":"Correlating Structure\nwith Function in Bacterial Multicomponent\nMonooxygenases and Related Diiron Proteins","volume":"39","author":"Sazinsky","year":"2006","journal-title":"Acc. Chem. Res."},{"issue":"10","key":"2026081008095729600_cit56","doi-asserted-by":"publisher","first-page":"2532","DOI":"10.1021\/acs.accounts.1c00147","article-title":"Linear Free Energy Relationships\nfor Enzymatic Reactions: Fresh Insight from a Venerable Probe","volume":"54","author":"Richard","year":"2021","journal-title":"Acc. Chem. Res."},{"issue":"2","key":"2026081008095729600_cit57","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/0005-2728(80)90179-6","article-title":"Linear Relation between\nRate and Thermodynamic Force in Enzyme-Catalyzed Reactions","volume":"591","author":"Van Der Meer","year":"1980","journal-title":"Biochim. Biophys. 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