Varghese roams from forests
to enzymes

Protecting nitrogenase

Nitrogen is abundant in the atmosphere yet scarce in the biosphere; only prokaryotes are equipped with the enzymes necessary to fix atmospheric nitrogen into bioavailable forms. To subvert this limitation and boost crop production, researchers are studying nitrogen-fixing enzymes with the goal of genetically engineering crop plants that can express nitrogenase of their own.

Iron-only nitrogenase, encoded by fewer genes than other nitrogen-fixing enzymes, is a promising candidate for this endeavor. However, it becomes inactive in the presence of oxygen; this barrier must be overcome for it to be expressed functionally in crops.

To explore how the structure of iron-only nitrogenase responds to oxygen, Varghese and colleagues at the James W. Murray lab at the department of life sciences at the Imperial College of London investigated the structure and oxygen-reducing role of Anf3, a protein associated with nitrogenase function.

By characterizing the crystal structure of Anf3 at atomic resolution, the team saw that its heme and flavin adenine dinucleotide cofactors were unexpectedly close to each other.

“The structure itself was a surprise,” Varghese said. “We knew (Anf3) had a heme and an FAD cofactor, but that they were so close together and that there was a cooperative effect was unexpected.”

Further experiments suggested that electron transfer between the two cofactors contributes to Anf3’s ability to reduce oxygen, thus protecting iron-only nitrogenase from being inactivated. Anf3 protein is a promising candidate for enhancing functional nitrogenase in aerobic environments.