Hydrogen-activation mechanism of [Fe] hydrogenase revealed by multi-scale modeling

Finkelmann, A. R., Senn, H. M. and Reiher, M. (2014) Hydrogen-activation mechanism of [Fe] hydrogenase revealed by multi-scale modeling. Chemical Science, 5(11), pp. 4474-4482. (doi: 10.1039/C4SC01605J)

Abstract

When investigating the mode of hydrogen activation by [Fe] hydrogenases, not only the chemical reactivity at the active site is of importance but also the large-scale conformational change between the so-called open and closed conformations, which leads to a special spatial arrangement of substrate and iron cofactor. To study H2 activation, a complete model of the solvated and cofactor-bound enzyme in complex with the substrate methenyl-H4MPT+ was constructed. Both the closed and open conformations were simulated with classical molecular dynamics on the 100 ns time scale. Quantum-mechanics/molecular-mechanics calculations on snapshots then revealed the features of the active site that enable the facile H2 cleavage. The hydroxyl group of the pyridinol ligand can easily be deprotonated. With the deprotonated hydroxyl group and the structural arrangement in the closed conformation, H2 coordinated to the Fe center is subject to an ionic and orbital push-pull effect and can be rapidly cleaved with a concerted hydride transfer to methenyl-H4MPT+. An intermediary hydride species is not formed.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Senn, Dr Hans
• Authors: Finkelmann, A. R., Senn, H. M., and Reiher, M.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Chemical Science
• Publisher: Royal Society of Chemistry
• ISSN: 2041-6520
• ISSN (Online): 2041-6539
• Copyright Holders: Copyright © 2014 The Royal Society of Chemistry
• First Published: First published in Chemical Science 5(11):4474-4482
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher