Ligand binding to the FeMo-cofactor: Structures of CO-bound and reactivated nitrogenase

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Science  26 Sep 2014:
Vol. 345, Issue 6204, pp. 1620-1623
DOI: 10.1126/science.1256679

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Making nitrogen available for biosynthesis

Nitrogen gas (N2) is abundant in Earth's atmosphere; however, it must be converted into a bioavailable form before it can be incorporated into biomolecules. The enzyme nitrogenase, which is made up of two metalloproteins, converts N2 into bioavailable ammonia. One of these, the MoFe-protein, contains a complex metal center, the FeMo cofactor, where the triple N2 bond is reduced. Understanding how nitrogenase achieves the reduction of N2 has been a long-term goal. Spatzal et al. present the structure of MoFe-protein bound to carbon monoxide (see the Perspective by Hogbom). Although this is an inhibitor rather than the natural substrate, the structure gives insight into how the FeMo metallocluster rearranges to achieve substrate reduction.

Science, this issue p. 1620


The mechanism of nitrogenase remains enigmatic, with a major unresolved issue concerning how inhibitors and substrates bind to the active site. We report a crystal structure of carbon monoxide (CO)–inhibited nitrogenase molybdenum-iron (MoFe)–protein at 1.50 angstrom resolution, which reveals a CO molecule bridging Fe2 and Fe6 of the FeMo-cofactor. The μ2 binding geometry is achieved by replacing a belt-sulfur atom (S2B) and highlights the generation of a reactive iron species uncovered by the displacement of sulfur. The CO inhibition is fully reversible as established by regain of enzyme activity and reappearance of S2B in the 1.43 angstrom resolution structure of the reactivated enzyme. The substantial and reversible reorganization of the FeMo-cofactor accompanying CO binding was unanticipated and provides insights into a catalytically competent state of nitrogenase.

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