A bound reaction intermediate sheds light on the mechanism of nitrogenase

Abstract

Sulfur steps aside for nitrogen Enzymatic conversion of molecular nitrogen to ammonia requires a dance of electrons and protons. The stage for that dance is the nitrogenase cofactor, a carefully constructed cluster of iron, sulfur, and carbon with homocitrate and, in some cases, bicarbonate appendages, as well as a secondary metal ion that defines the class of enzyme. The question of how this cofactor binds nitrogen has been vexingly difficult to answer. Sippel et al. report a high-resolution structure of the vanadium nitrogenase with a light atom, interpreted as nitrogen, bound to the FeV cofactor. A sulfur atom is displaced from the cofactor in this structure and is observed resting in a holding site formed by rearrangement of a glutamine residue. The putative bridging nitrogen atom suggests that diatomic nitrogen may bind to the cluster in a head-on manner, with the glutamine side chain stabilizing protonated intermediates as they are reduced. Science , this issue p. 1484