Catalysis and structure of nitrogenases

In providing bioavailable nitrogen as building blocks for all classes of biomacromolecules, biological nitrogen fixation is an essential process for all organismic life. Only a single enzyme, nitrogenase, performs this task at ambient conditions and with ATP as an energy source. The assembly of the complex iron-sulfur enzyme nitrogenase and its catalytic mechanism remains a matter of intense study. Recent progress in the structural analysis of the three known isoforms of nitrogenase-differentiated primarily by the heterometal in their active site cofactor-has revealed a degree of structural plasticity of these clusters that suggest two distinct binding sites for substrates and reaction intermediates. A mechanistic proposal based on this finding integrates most of the available experimental data. Furthermore, the first applications of high-resolution cryo-electron microscopy have highlighted further dynamic conformational changes. Structures obtained under turnover conditions support the proposed alternating half-site reactivity in the C₂-symmetric nitrogenase complex.