DFT Study on Nitrite Reduction Mechanism in Copper-Containing Nitrite Reductase

Area of Science:

• Biochemistry
• Environmental Science
• Computational Chemistry

Background:

• Dissimilatory nitrite reduction by copper-containing nitrite reductase (CuNiR) is crucial for the geobiochemical nitrogen cycle.
• Proton-coupled electron transfer (PCET) is a fundamental process in enzymatic reactions, including nitrite reduction.
• Understanding the mechanism of CuNiR is vital for comprehending nitrogen cycling and enzyme catalysis.

Purpose of the Study:

• To investigate the geometric structure of bound nitrite and the reduction mechanism of CuNiR using computational methods.
• To elucidate the proton transfer pathway, identify key residues, and determine their roles in the catalytic mechanism.
• To explore the interplay between electron transfer, proton transfer, and substrate binding in CuNiR.

Main Methods:

• Density functional theory (DFT) calculations were employed to model the nitrite reduction reaction on CuNiR.
• Analysis of the geometric structure of bound nitrite and transition states.
• Identification of key amino acid residues and hydrogen bonding networks involved in catalysis.

Main Results:

• The reduction of the T2 copper site was found to promote proton transfer during nitrite reduction.
• A hydrogen bond network surrounding the nitrite binding site plays a critical role in stabilizing substrate binding.
• This hydrogen bond network also significantly facilitates the proton transfer to the bound nitrite molecule.

Conclusions:

• The study clarifies the mechanism of nitrite reduction by CuNiR, highlighting the importance of PCET.
• Key residues and the hydrogen bond network are essential for both substrate binding and efficient proton transfer.
• These findings provide insights into the catalytic strategies employed by metalloenzymes in biogeochemical cycles.