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

Research output: Contribution to journalArticle

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.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology
Original languageEnglish
Pages (from-to)383-394
JournalJournal of Biological Inorganic Chemistry
Volume21
Issue number3
Early online date2016 Mar 3
Publication statusPublished - 2016
Publication categoryResearch
Peer-reviewedYes

Total downloads

No data available