Pagina 1 di 1
Computational investigation of carbon monoxide dehydrogenase’s biological diversity
Exploring Nature’s mechanisms for CO2 fixation is an important and timely research topic, considering the current environmental crisis linked to increased levels of greenhouse gasses. Anaerobic microorganisms use nickel-iron carbon monoxide dehydrogenase (NiFe-CODH) metalloenzymes to catalyze CO2 reduction and CO oxidation. NiFe-CODHs… Leggi tutto play key physiological roles, such as enabling growth using the reducing power of CO and fixing CO2 to generate acetylCoA(1). However, these enzymes proved difficult to study and their catalytic mechanism remains unclear. Although only a tiny fraction of the vast biodiversity of NiFe-CODHs has been explored, it has already revealed their intriguing functional biodiversity. Interestingly, these enzymes have the same inorganic active site, surrounded by conserved residues, but homologous NiFe-CODHs have different catalytic properties (i.e. catalytic rates, substrate affinities, and, most importantly, oxygen resistance). These properties must be determined by the protein scaffold, in a way that is still unknown. The host laboratory showed how informative quantum and molecular mechanics methods are to investigate redox metalloenzymes such as NiFe-CODHs and hydrogenases(2,3), paving the way for this project. Focusing on three model enzymes, and using a computational approach, this project has two main objectives: first, fully elucidate the catalytic mechanism of NiFe-CODHs and the protein scaffold’s role in controlling catalytic properties; second, clarify the O2 inhibition mechanisms, still poorly understood, and identify the key residues involved in O2 resistance. These findings will contribute to the understanding of the NiFe-CODH’s physiological functions, and will help in designing catalysts to fix CO2.