Nitrogenase: a general hydrogenator of small molecules

Area of Science:

• Biochemistry and Bioinorganic Chemistry
• Catalysis and Enzyme Mechanisms
• Computational Chemistry and Molecular Modeling

Background:

• Nitrogenase is a crucial enzyme responsible for biological nitrogen fixation, converting atmospheric nitrogen (N2) into ammonia (NH3).
• Beyond N2 reduction, nitrogenase exhibits promiscuity, catalyzing the hydrogenation of various small molecules, often requiring multiple electrons and protons.
• The active site, the iron-molybdenum cofactor (FeMo-co), possesses a unique structure that is key to its catalytic versatility.

Purpose of the Study:

• To propose a unified mechanistic model explaining the diverse hydrogenation reactions catalyzed by nitrogenase.
• To rationalize the role of the FeMo-co structure in enabling these multiple catalytic functions.
• To provide a theoretical framework for understanding nitrogenase's broad substrate scope.

Main Methods:

• Extensive density functional calculations (DFT) were employed to simulate reaction pathways.
• Molecular dynamics simulations were used to explore the dynamic aspects of the catalytic process.
• The proposed mechanism was developed by integrating computational findings with known experimental data.

Main Results:

• A general mechanism involving serial proton and electron transfer to the FeMo-co active site was elucidated.
• Generated hydrogen atoms populate specific sulfur and iron atoms within the FeMo-co reaction domain.
• A contiguous binding of substrate and hydrogen atoms facilitates efficient H-atom transfer to form products, explaining N2 fixation and other hydrogenations.

Conclusions:

• The proposed mechanistic paradigm provides a unified explanation for nitrogenase's ability to catalyze N2 reduction and other hydrogenation reactions.
• The unique structural features of FeMo-co are rationalized as being essential for its function as a general hydrogenation catalyst.
• The study suggests specific experiments to further test and validate the proposed catalytic mechanism.