Sulfide release and rebinding in the mechanism for nitrogenase.

Nitrogenases are the only enzymes that activate the strong triple bond in N ₂ . The mechanism for the activation has been very difficult to determine in spite of decades of work. In previous modeling studies it has been suggested that the mechanism for nitrogen activation starts out by four pre-activation steps (A ₀ -A ₄ ) before catalysis. That suggestion led to excellent agreement with experimental Elecrtron Paramagnetic Resonance (EPR) observations in the step where N ₂ becomes protonated (E ₄ ). An important part of the pre-activation is that a sulfide is released. In the present paper, the details of the pre-activation are modeled, including the release of the sulfide. Several possible transition states for the release have been obtained. An A ₄ (E ₀ ) state is reached which is very similar to the E ₄ state. For completeness, the steps going back from A ₄ (E ₀ ) to A ₀ after catalysis are also modeled, including the insertion of a sulfide.
(© 2024 The Author(s). Journal of Computational Chemistry published by Wiley Periodicals LLC.)