PNNL

Abstract

The reduction of dinitrogen (N2) to ammonia (NH3) as catalyzed by the enzyme nitrogenase involves a complex series of events, including ATP hydrolysis, electron transfer, and activation of metal clusters for N2 reduction. There is early evidence that an essential part of the mechanism involves the transduction of information between the nitrogenase component proteins through conformational dynamics. Here, millisecond time-resolved hydrogen-deuterium exchange mass spectrometry (HDX-MS) was used to unravel peptide-level correlated and anti-correlated protein motions during the reaction cycle. Normal mode analysis calculations provide insights into the specific signal transduction pathways that relay information across protein interfaces at distances of 100 Å on a millisecond timescale. It is shown that conformational changes induced by protein docking are rapidly transduced to the active site, suggesting a specific mechanism for activating the metal cofactor in the enzyme active site.