{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Jiang H"],"funding":["China Scholarship Council","Vetenskapsr?det","Lunds Universitet"],"pagination":["19433-19445"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10698722"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["62(48)"],"pubmed_abstract":["Nitrogenase is the only enzyme that can cleave the strong triple bond in N<sub>2</sub>, making nitrogen available for biological life. There are three isozymes of nitrogenase, differing in the composition of the active site, viz., Mo, V, and Fe-nitrogenase. Recently, the first crystal structure of Fe-nitrogenase was presented. We have performed the first combined quantum mechanical and molecular mechanical (QM/MM) study of Fe-nitrogenase. We show with QM/MM and quantum-refinement calculations that the homocitrate ligand is most likely protonated on the alcohol oxygen in the resting E<sub>0</sub> state. The most stable broken-symmetry (BS) states are the same as for Mo-nitrogenase, i.e., the three Noodleman BS7-type states (with a surplus of β spin on the eighth Fe ion), which maximize the number of nearby antiferromagnetically coupled Fe-Fe pairs. For the E<sub>1</sub> state, we find that protonation of the S2B μ<sub>2</sub> belt sulfide ion is most favorable, 14-117 kJ/mol more stable than structures with a Fe-bound hydride ion (the best has a hydride ion on the Fe2 ion) calculated with four different density-functional theory methods. This is similar to what was found for Mo-nitrogenase, but it does not explain the recent EPR observation that the E<sub>1</sub> state of Fe-nitrogenase should contain a photolyzable hydride ion. For the E<sub>1</sub> state, many BS states are close in energy, and the preferred BS state differs depending on the position of the extra proton and which density functional is used."],"journal":["Inorganic chemistry"],"pubmed_title":["Protonation of Homocitrate and the E<sub>1</sub> State of Fe-Nitrogenase Studied by QM/MM Calculations."],"pmcid":["PMC10698722"],"funding_grant_id":["2022-04978","2018-05973","2018-05003"],"pubmed_authors":["Lundgren KJM","Jiang H","Ryde U"],"additional_accession":[]},"is_claimable":false,"name":"Protonation of Homocitrate and the E<sub>1</sub> State of Fe-Nitrogenase Studied by QM/MM Calculations.","description":"Nitrogenase is the only enzyme that can cleave the strong triple bond in N<sub>2</sub>, making nitrogen available for biological life. There are three isozymes of nitrogenase, differing in the composition of the active site, viz., Mo, V, and Fe-nitrogenase. Recently, the first crystal structure of Fe-nitrogenase was presented. We have performed the first combined quantum mechanical and molecular mechanical (QM/MM) study of Fe-nitrogenase. We show with QM/MM and quantum-refinement calculations that the homocitrate ligand is most likely protonated on the alcohol oxygen in the resting E<sub>0</sub> state. The most stable broken-symmetry (BS) states are the same as for Mo-nitrogenase, i.e., the three Noodleman BS7-type states (with a surplus of β spin on the eighth Fe ion), which maximize the number of nearby antiferromagnetically coupled Fe-Fe pairs. For the E<sub>1</sub> state, we find that protonation of the S2B μ<sub>2</sub> belt sulfide ion is most favorable, 14-117 kJ/mol more stable than structures with a Fe-bound hydride ion (the best has a hydride ion on the Fe2 ion) calculated with four different density-functional theory methods. This is similar to what was found for Mo-nitrogenase, but it does not explain the recent EPR observation that the E<sub>1</sub> state of Fe-nitrogenase should contain a photolyzable hydride ion. For the E<sub>1</sub> state, many BS states are close in energy, and the preferred BS state differs depending on the position of the extra proton and which density functional is used.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2025-04-26T11:46:50.079Z","creation":"2025-04-06T13:48:14.51Z"},"accession":"S-EPMC10698722","cross_references":{"pubmed":["37987624"],"doi":["10.1021/acs.inorgchem.3c02329"]}}