  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.
