A bound reaction intermediate sheds light on the mechanism of nitrogenase
Sippel D, Rohde M, Netzer J, Trncik C, Gies J, Grunau K, Djurdjevic I, Decamps L, Andrade SLA, Einsle O.
Reduction of N2 by nitrogenases occurs at an organometallic Fe-cofactor that commonly also contains either molybdenum or vanadium. The well-characterized resting state of the cofac-tor does not bind substrate, so that its mode of action remains enigmatic. CO was recently found to replace a bridging sulfide, but the mechanistic relevance was unclear. Here we report the structural analysis of vanadium nitrogenase with a bound intermediate, interpreted as a µ2-bridging N-H that implies the site and mode of substrate binding to the cofactor. Binding results in a flip of amino acid Q176 that hydrogen-bonds the ligand and creates a holding position for the displaced sulfide. The intermediate represents state E6 or E7 of the Thorneley-Lowe model and provides clues for the remainder of the catalytic cycle.
