Nitrogenase, the bacterial catalyst for N2 fixation, is a multi-subunit metalloenzyme comprising two electron carrier Fe proteins and one catalytic core MoFe protein. This complex catalyzes the reduction of dinitrogen (N2) to two ammonia (NH3) molecules with electrons provided by the Fe protein upon adenosine triphosphate (ATP) hydrolysis. Association of the Fe protein with two bound ATP molecules with each αβ half of the α2β2 MoFe protein initiates a series of synchronized events, involving large-scale conformational motions that result in the transfer of an electron from the Fe protein ending on the [7Fe-9S-Mo-homocitrate] catalytic cofactor (MoFe-co) via the [8Fe-7S] P-cluster in the MoFe protein. The hydrolysis of two ATP to adenosine diphosphate (ADP) and inorganic phosphate (Pi) induces the dissociation of the Fe protein (oxidized and with two bound ADP) from the MoFe protein (reduced by one electron). This cascade of events must be repeated eight times for every N2 molecule. Here, we conducted an extensive investigation of the conformational dynamics of the nitrogenase complex based on multi-microsecond-long molecular dynamics simulations of both the ATP- and ADP-bound complex, and graph-based analysis of the energy flow in the nitrogenase complex. The motion of the Fe protein on the surface of the MoFe protein is strongly coupled with possible electron transfer pathways as identified from semi-empirical methods. We also observed that the two halves of nitrogenase do not operate independently, but rather are mechanically linked via conformational changes that cause them to anti-cooperate, as suggested by recent kinetic measurements.

Mechanical coupling in the nitrogenase complex

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.