Studies on the hydrogenation steps of the nitrogen molecule at theAzotobacter vinelandii nitrogenase site

Stavrev, Krassimir K.; Zerner, Michael C.

doi:10.1002/(sici)1097-461x(1998)70:6<1159::aid-qua5>3.0.co;2-z

Cited by 48 publications

(6 citation statements)

References 43 publications

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“…In the E 1 state, we find that the most favorable protonation site is S2B and this also agrees with most previous theoretical studies. ,,− , However, for the E 2 –E 4 states, we find new preferred protonation states that have not been suggested previously and, moreover, the predictions are strongly dependent on which DFT method is used to calculate the relative energies. With the pure TPSS functional, we obtain structures with hydride ions on the Fe ions, typically with several structures close in energies, indicating that the hydride ions may move quite freely within the cluster.…”

Section: Discussionsupporting

confidence: 91%

“…Predictions of the relative energies of the best protonation states for E 4 differ by >300 kJ/mol. This is the reason for the recent controversy between Siegbahn and the Hoffman group about the best protonation of the E 4 state , and is probably also an important reason for the many differing mechanisms suggested for the enzyme. ,,− ,− Undoubtedly, we urgently need more-accurate QM methods that can decide which DFT approaches give the more-accurate energies. At present, we can only point out that pure functionals give more-accurate structures of the resting state (compared to the crystal structure) and a protonation of the E 4 state that is closer to the interpretation of the experiments (with two bridging hydride ions), whereas B3LYP seems to give more reasonable energies of states involving H 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Nitrogenase has also been extensively studied by computational methods. ,,− ,− Earlier studies were hampered by the fact that the central carbide ion in the FeMo cluster was not identified until 2014, − and that the redox state of the cluster was not settled until 2017. − Moreover, earlier studies did not involve the loading of the active site by four electrons and protons before the actual reaction could occur. However, even among the latest quantum mechanical (QM) studies, there is no agreement among the reaction mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Protonation and Reduction of the FeMo Cluster in Nitrogenase Studied by Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations

Cao

Caldararu

Ryde

2018

J. Chem. Theory Comput.

193

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We have performed a systematic computational study of the relative energies of possible protonation states of the FeMo cluster in nitrogenase in the E0-E4 states, i.e. the resting state and states with 1-4 electrons and protons added but before N2 binds. We use the combined quantum mechanics and molecular mechanics (QM/MM) approach, including the complete solvated heterotetrameric enzyme in the calculations. The QM system consisted of 112 atoms, i.e. the full FeMo cluster, as well all groups forming hydrogen bonds to it within 3.5 Å. It was treated with either the TPSS-D3 or B3LYP-D3 methods with the def2-SV(P) or def2-TZVPD basis sets. For each redox state, we calculated relative energies of at least 50 different possible positions for the proton, added to the most stable protonation state of the level with one electron less. We show quite conclusively that the resting E0 state is not protonated using quantum refinement and by comparing geometries to the crystal structure. The E1 state is protonated on S2B, in agreement with most previous computational studies. However, for the E2-E4 states, the two QM methods give diverging results, with relative energies that differ by over 300 kJ/mol for the most stable E4 states. TPSS favours hydride ions binding to the Fe ions. The first bridges Fe2 and Fe6, whereas the next two bind terminally to either Fe4, Fe5 or Fe6 with nearly equal energies. On the other hand, B3LYP disfavours hydride ions and instead suggests that 1-3 protons bind to the central carbide ion.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protonation and Reduction of the FeMo Cluster in Nitrogenase Studied by Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations

Cao

Caldararu

Ryde

2018

J. Chem. Theory Comput.

193

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“…Many computational studies of nitrogenase have been presented, with the hope to give a detailed atomistic description of the various reaction steps. ,,− ,,− Unfortunately, they have given strongly divergent results. For example, some studies have suggested that N 2 is protonated alternatively on both N atoms, giving diazene (HNNH) and hydrazine (H 2 NNH 2 ) as intermediates, , whereas others have suggested that the distal N atom is first triply protonated and dissociates as NH 3 before the second N atom is protonated. , Likewise, some studies have suggested that N 2 binds end-on to one or two Fe ions, , whereas others have suggested that it binds side-on to two Fe ions or that it forms a covalent bond with the central carbide ion. , …”

Section: Introductionmentioning

confidence: 99%

What Is the Structure of the E₄ Intermediate in Nitrogenase?

Cao

Ryde

2020

J. Chem. Theory Comput.

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Nitrogenase is the only enzyme that can cleave the strong triple bond in N2. The active site contains a complicated MoFe7S9C cluster. It is believed that it needs to accept four protons and electrons, forming the E4 state, before it can bind N2. However, there is no consensus on the atomic structure of the E4 state. Experimental studies indicate that it should contain two hydride ions bridging two pairs of Fe ions, and it has been suggested that both hydride ions as well as the two protons bind on the same face of the cluster. On the other hand, density functional theory (DFT) studies have indicated that it is energetically more favorable with either three hydride ions or with a triply protonated carbide ion, depending on the DFT functional. We have performed a systematic combined quantum mechanical and molecular mechanical (QM/MM) study of possible E4 states with two bridging hydride ions. Our calculations suggest that the most favorable structure has hydride ions bridging the Fe2/6 and Fe3/7 ion pairs. In fact, such structures are 14 kJ/mol more stable than structures with three hydride ions, showing that pure DFT functionals give energetically most favorable structures in agreement with experiments. An important reason for this finding is that we have identified a new type of broken-symmetry state that involves only two Fe ions with minority spin, in contrast to the previously studied states with three Fe ions with minority spin. The energetically best structures have the two hydride ions on different faces of the FeMo cluster, whereas better agreement with ENDOR data is obtained if they are on the same face; such structures are only 6–22 kJ/mol less stable.

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“…Based on computational results, a number of different mechanisms have been proposed2–23 for the biological reductions. Several early papers appeared before Rees and coworkers1 revealed in 2002 that an atom resides in the center of the FeMo cofactor 56–60. A paper by Siegbahn et al59 in 1998 found that adding a hydrogen to a bridging sulfur significantly increased the binding energy of N 2 to iron.…”

Section: Introductionmentioning

confidence: 99%

Modeling the nitrogenase FeMo cofactor with high‐spin Fe₈S₉X⁺ (XN, C) clusters. Is the first step for N₂ reduction to NH₃ a concerted dihydrogen transfer?

McKee

2007

J Comput Chem

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A high-spin Fe(8)S(9)X(+) (X=N, C) cluster is used to model the reduction of molecular nitrogen to ammonia by the nitrogenase FeMo cofactor at the B3LYP/6-311G(d,p)/ECP(Fe,SDD) level of theory. A total of seventy-three structures were optimized (including three transition state optimizations) to explore the structure and energetic of N(2), C(2)H(2), and CO coordination to the Fe(8)S(9)X(+) cluster. After three protonation-reduction (PR) steps (modeled by addition of hydrogen atoms), N(2), C(2)H(2), and CO are predicted to bind to a Fe atom in the exo (cage does not open) position with binding energies of 7.6, 14.7, and 11.7 kcal/mol. With additional PR steps the coordination number of the core nitrogen atom is reduced from six to five and the bridging thiol group becomes a terminal SH(2) group. The fifth and sixth PR steps occur on the core nitrogen and the open Fe site. Coordination of N(2) is enhanced after six PR steps to give an intermediate ideally suited for a concerted dihydrogen transfer from the Fe and core nitrogen atoms to the coordinated N(2). The identity of the central atom (nitrogen or carbon) has only a minor effect on the reaction steps.

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Studies on the hydrogenation steps of the nitrogen molecule at theAzotobacter vinelandii nitrogenase site

Cited by 48 publications

References 43 publications

Protonation and Reduction of the FeMo Cluster in Nitrogenase Studied by Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations

Protonation and Reduction of the FeMo Cluster in Nitrogenase Studied by Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations

What Is the Structure of the E₄ Intermediate in Nitrogenase?

Modeling the nitrogenase FeMo cofactor with high‐spin Fe₈S₉X⁺ (XN, C) clusters. Is the first step for N₂ reduction to NH₃ a concerted dihydrogen transfer?

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Studies on the hydrogenation steps of the nitrogen molecule at theAzotobacter vinelandii nitrogenase site

Cited by 48 publications

References 43 publications

Protonation and Reduction of the FeMo Cluster in Nitrogenase Studied by Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations

Protonation and Reduction of the FeMo Cluster in Nitrogenase Studied by Quantum Mechanics/Molecular Mechanics (QM/MM) Calculations

What Is the Structure of the E4 Intermediate in Nitrogenase?

Modeling the nitrogenase FeMo cofactor with high‐spin Fe8S9X+ (XN, C) clusters. Is the first step for N2 reduction to NH3 a concerted dihydrogen transfer?

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What Is the Structure of the E₄ Intermediate in Nitrogenase?

Modeling the nitrogenase FeMo cofactor with high‐spin Fe₈S₉X⁺ (XN, C) clusters. Is the first step for N₂ reduction to NH₃ a concerted dihydrogen transfer?