Nitrogen Fixation

Nitrogenase is the only known enzyme system that is able to cleave the stable triple bond of the inert dinitrogen molecule. Dinitrogen not only makes up 78% of Earth's atmosphere, but it also forms a sink for the element, holding 99% of all [N] cycling through the biosphere at any given time. The chemical necessity to tap into this reservoir is only achieved by bacteria, while the growth of higher organisms, in particular plants in large-scale agriculture, is frequently limited by the ability of nitrogen. This problem is commonly addressed by fertilization using fixed nitrogen generated through the industrial Haber-Bosch process.

Nature's solution, nitrogenase, catalyzed the reductive cleavage of dinitrogen at ambient temperature and pressure, albeit at a high cost of metabolic energy in the form of ATP. The reaction takes place at the FeMo cofactor, the largest and most complex metal center known to biology. Our work is focused on understanding the properties of FeMo cofactor, its architecture and mode of operation. We thus aim to generate the knowledge required to understand, modify and - eventually - utilize this unique molecular machine.

References:

• Spatzal, T., Aksoyoglu, M., Zhang, L., Andrade, S.L.A., Schleicher, E., Weber, S., Rees, D.C. & Einsle, O. (2011) Evidence for Interstitial Carbon in Nitrogenase FeMo Cofactor.  Science, 334, 940.
• Andrade, S. L., Ribbe, M. W., Hu, Y. & Einsle, O. (2008) Recent Advances on Nitrogenase. In:Handbook of Metalloproteins (Messerschmidt, A., ed.) John Wiley & Sons, New York.
• Einsle, O., Andrade, S. L., Dobbek, H., Meyer, J. & Rees, D. C. (2007) Assignment of Individual Metal Redox States in a Metalloprotein by Crystallographic Refinement at Multiple X-ray Wavelengths. 
J. Am. Chem. Soc., 129, 2210-2211.
• Rees, D. C., Tezcan, F. A., Haynes, C. A., Walton, M. Y., Andrade, S. L., Einsle, O. & Howard, J. B. (2005) Structural Basis of Nitrogen Fixation. 
Philos. Transact. A Math. Phys. Eng. Sci., 363, 971-984.
• Corbett, M. C., Tezcan, F. A., Einsle, O., Walton, M. Y., Rees, D. C. Latimer, M. J., Hedman, B. & Hodgson, K. O. (2005) Mo K- and L-edge X-ray absorption spectroscopic study of the ADP-AlF₄^- stabilized nitrogenase complex: Comparison with MoFe protein in solution and single crystal. 
J. Synchrotron Rad., 12, 28-34.
• Schmid, B., Einsle, O., Willing, A., Yoshida, M., Howard, J. & Rees, D. C. (2002) Biochemical and structural characterization of the crosslinked complex of nitrogenase: com-parison to the ADP-AlF₄^--stabilized structure.
Biochemistry, 41, 15557-15565.
• Einsle, O., Tezcan, F. A., Andrade, S. L., Schmid, B., Yoshida, M., Howard, J. B. & Rees, D. C. (2002) Nitrogenase MoFe protein at 1.16 Å resolution: A central ligand in the FeMo cofactor. 
Science, 297, 1696-1700.
• Schmid, B., Ribbe, M. W., Einsle, O., Yoshida, M., Thomas, L. M., Rees, D. C. & Burgess, B. K. (2002) Implications for metalloprotein assembly from the structure of a FeMo cofactor deficient nitrogenase MoFe protein. 
Science, 296, 352-356.