GuestSeminars
Zoom Session
Add to Calendar 2023-11-30 14:00:00 2023-11-30 15:00:00 GuestSeminars@UCIBIO | Oliver Einsle Nitrogenase: Unraveling an Impossible Enzyme Mechanism Oliver Einsle, Institut für Biochemie, Albert-Ludwigs-Universität Freiburg, Germany Host: Sofia Pauleta, UCIBIO, NOVA   ZOOM link: https://ucibio.pt/l/GuestSeminars   Abstract: In the biological fixation of nitrogen, the unique, Mo- or V- and Fe-containing catalytic cofactor generates a highly reduced and reactive species that converts inert substrate molecules such as cyanide, carbon monoxide and of course the physiological substrate dinitrogen (N2). Contrary to the industrial HaberBosch process, this reaction occurs at ambient temperature and pressure, making the catalytic site a highly interesting target for basic research, biotechnological application and as an inspiration for the design of new catalysts. Activation of substrates is achieved by the stoichiometric reductive elimination of H2 after a four-electron reduction of the cofactor. A series of studies in recent years has shown that a particular position on the cofactor can reversible eliminate a µ2-bridging sulfide, opening a dinuclear binding site formed by Fe2 and Fe6 of the cluster and providing experimental evidence for the mode and position of ligand binding to the cofactor.   The definition of a precise binding site for substrates and inhibitors – and also for the hydride ions generated during the charging process – now provides a basis for the integration of biochemical and biophysical data with theoretical calculations. Binding of CO to the enzyme allowed to outline a precise reaction mechanism and structural studies of all known nitrogenase isoforms now provide unprecedented detail to elucidate the reactivity and mechanism of the enigmatic nitrogenase enzymes.   References: Spatzal, T., Perez, K. A., Einsle, O., Howard, J. B. & Rees, D. C. (2014). Science 345, 1620-1623. Sippel, D. & Einsle, O. (2017). Nature Chem. Biol. 13, 956. Sippel, D., Rohde, M., Netzer, J., Trncik, C., Gies, J., Grunau, K., Djurdjevic, I., Decamps, L., Andrade, S. L. A. & Einsle, O. (2018). Science 359, 1484-1489. Rohde. M., Sippel, D., Trncik, C., Andrade, S.L.A. & Einsle, O. (2018). Biochemistry 57, 5497. Rohde, M., Grunau, K. & Einsle, O. (2020). Angew. Chem. Intl. Ed. 59, 23626-23630. Einsle, O. & Rees, D.C. (2020). Chem. Rev. 120, 4969-5007. Rohde, M., Laun, K., Zebger, I., Stripp, S.T. & Einsle, O. (2021). Science Adv. 7, eabg4474.   Short CV: Oliver Einsle (b. 1970) studied Biology in Konstanz, Germany, and then moved to the Max Planck Institute for Biochemistry in Martinsried, Germany, to work with Robert Huber and Peter Kroneck on cytochrome c nitrite reductase. In 2001 he joined the laboratory of Doug Rees at Caltech, USA, to study nitrogenase, and in 2003 he took on a position as junior professor for protein crystallography in Göttingen, Germany. Since 2008 he is full professor of Biochemistry in Freiburg, Germany, and director of the Institute of Biochemistry in the faculty of Chemistry and Pharmacy. His group has made seminal contributions to the structural and functional characterization of various metalloproteins, including nitrogenase and nitrous oxide reductase, but also multiheme cytochromes c. A second line of research is centered on the study of integral membrane proteins, in particular bacterial transporters and channels. From 2018 to 2021, he was the Dean of the Faculty of Chemistry and Pharmacy. He received the Early Career Award of the Society of Bioinorganic Chemistry and is a Member of the German National Academy of Sciences Leopoldina. Zoom Session UCIBIO info@simbiose.com Europe/Lisbon public
oliver einsle

Nitrogenase: Unraveling an Impossible Enzyme Mechanism

Oliver Einsle, Institut für Biochemie, Albert-Ludwigs-Universität Freiburg, Germany


Host: Sofia Pauleta, UCIBIO, NOVA

 

ZOOM link: https://ucibio.pt/l/GuestSeminars

 

Abstract:

In the biological fixation of nitrogen, the unique, Mo- or V- and Fe-containing catalytic cofactor generates a highly reduced and reactive species that converts inert substrate molecules such as cyanide, carbon monoxide and of course the physiological substrate dinitrogen (N2). Contrary to the industrial HaberBosch process, this reaction occurs at ambient temperature and pressure, making the catalytic site a highly interesting target for basic research, biotechnological application and as an inspiration for the design of new catalysts. Activation of substrates is achieved by the stoichiometric reductive elimination of H2 after a four-electron reduction of the cofactor. A series of studies in recent years has shown that a particular position on the cofactor can reversible eliminate a µ2-bridging sulfide, opening a dinuclear binding site formed by Fe2 and Fe6 of the cluster and providing experimental evidence for the mode and position of ligand binding to the cofactor.
 

The definition of a precise binding site for substrates and inhibitors – and also for the hydride ions generated during the charging process – now provides a basis for the integration of biochemical and biophysical data with theoretical calculations. Binding of CO to the enzyme allowed to outline a precise reaction mechanism and structural studies of all known nitrogenase isoforms now provide unprecedented detail to elucidate the reactivity and mechanism of the enigmatic nitrogenase enzymes.

 

References:
Spatzal, T., Perez, K. A., Einsle, O., Howard, J. B. & Rees, D. C. (2014). Science 345, 1620-1623. Sippel, D. & Einsle, O. (2017). Nature Chem. Biol. 13, 956.
Sippel, D., Rohde, M., Netzer, J., Trncik, C., Gies, J., Grunau, K., Djurdjevic, I., Decamps, L., Andrade, S. L. A. & Einsle, O. (2018). Science 359, 1484-1489.
Rohde. M., Sippel, D., Trncik, C., Andrade, S.L.A. & Einsle, O. (2018). Biochemistry 57, 5497. Rohde, M., Grunau, K. & Einsle, O. (2020). Angew. Chem. Intl. Ed. 59, 23626-23630.
Einsle, O. & Rees, D.C. (2020). Chem. Rev. 120, 4969-5007.
Rohde, M., Laun, K., Zebger, I., Stripp, S.T. & Einsle, O. (2021). Science Adv. 7, eabg4474.

 

Short CV:

Oliver Einsle (b. 1970) studied Biology in Konstanz, Germany, and then moved to the Max Planck Institute for Biochemistry in Martinsried, Germany, to work with Robert Huber and Peter Kroneck on cytochrome c nitrite reductase. In 2001 he joined the laboratory of Doug Rees at Caltech, USA, to study nitrogenase, and in 2003 he took on a position as junior professor for protein crystallography in Göttingen, Germany. Since 2008 he is full professor of Biochemistry in Freiburg, Germany, and director of the Institute of Biochemistry in the faculty of Chemistry and Pharmacy. His group has made seminal contributions to the structural and functional characterization of various metalloproteins, including nitrogenase and nitrous oxide reductase, but also multiheme cytochromes c. A second line of research is centered on the study of integral membrane proteins, in particular bacterial transporters and channels. From 2018 to 2021, he was the Dean of the Faculty of Chemistry and Pharmacy. He received the Early Career Award of the Society of Bioinorganic Chemistry and is a Member of the German National Academy of Sciences Leopoldina.

GuestSeminars@UCIBIO | Oliver Einsle