Protonation states of intermediates in the reaction mechanism of [NiFe] hydrogenase studied by computational methods

Original Paper

Abstract

The [NiFe] hydrogenases catalyse the reversible conversion of H2 to protons and electrons. The active site consists of a Fe ion with one carbon monoxide, two cyanide, and two cysteine (Cys) ligands. The latter two bridge to a Ni ion, which has two additional terminal Cys ligands. It has been suggested that one of the Cys residues is protonated during the reaction mechanism. We have used combined quantum mechanical and molecular mechanics (QM/MM) geometry optimisations, large QM calculations with 817 atoms, and QM/MM free energy simulations, using the TPSS and B3LYP methods with basis sets extrapolated to the quadruple zeta level to determine which of the four Cys residues is more favourable to protonate for four putative states in the reaction mechanism, Ni-SIa, Ni-R, Ni-C, and Ni-L. The calculations show that for all states, the terminal Cys-546 residue is most easily protonated by 14–51 kJ/mol, owing to a more favourable hydrogen-bond pattern around this residue in the protein.

Keywords

[NiFe] hydrogenase Protonation Reaction mechanism QM/MM Big-QM calculations 

Supplementary material

775_2016_1348_MOESM1_ESM.pdf (118 kb)
Supplementary material 1 (PDF 117 kb)

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Copyright information

© SBIC 2016

Authors and Affiliations

  1. 1.Department of Theoretical ChemistryLund UniversityLundSweden

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