10.3389/fchem.2018.00164.s001 Andrés M. Escorcia Andrés M. Escorcia Matthias Stein Matthias Stein Data_Sheet_1_QM/MM Investigation of the Role of a Second Coordination Shell Arginine in [NiFe]-Hydrogenases.PDF Frontiers 2018 hydrogen conversion enzyme QM/MM amino acid substitution catalysis 2018-05-15 04:29:33 Dataset https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_QM_MM_Investigation_of_the_Role_of_a_Second_Coordination_Shell_Arginine_in_NiFe_-Hydrogenases_PDF/6268022 <p>[NiFe]-hydrogenases are highly efficient catalysts for the heterolytic splitting of molecular hydrogen (H<sub>2</sub>). The heterobimetallic cysteine-coordinated active site of these enzymes is covered by a highly conserved arginine residue, whose role in the reaction is not fully resolved yet. The structural and catalytic role of this arginine is investigated here using QM/MM calculations with various exchange-correlation functionals. All of them give a very consistent picture of the thermodynamics of H<sub>2</sub> oxidation. The concept of the presence of a neutral arginine and its direct involvement as a Frustrated Lewis Pair (FLP) in the reaction is critically evaluated. The arginine, however, would exist in its standard protonation state and perform a critical role in positioning and slightly polarizing the substrate H<sub>2</sub>. It is not directly involved in the heterolytic processing of H<sub>2</sub> but guides its approach and reduces its flexibility during binding. Upon substitution of the positively charged arginine by a charge-conserving lysine residue, the H<sub>2</sub> binding position remains unaffected. However, critical hydrogen bonding interactions with nearby aspartate residues are lost. In addition, the H<sub>2</sub> polarization is unfavorable and the reduced side-chain volume may negatively affect the kinetics of the catalytic process.</p>