QM/MM Investigation of the Role of a Second Coordination Shell Arginine in [NiFe]-Hydrogenases.

Andrés M Escorcia,Matthias Stein

doi:10.3389/fchem.2018.00164

Andrés M Escorcia, Matthias Stein

Open Access

https://doi.org/10.3389/fchem.2018.00164

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Abstract

[NiFe]-hydrogenases are highly efficient catalysts for the heterolytic splitting of molecular hydrogen (H2). 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 H2 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 H2. It is not directly involved in the heterolytic processing of H2 but guides its approach and reduces its flexibility during binding. Upon substitution of the positively charged arginine by a charge-conserving lysine residue, the H2 binding position remains unaffected. However, critical hydrogen bonding interactions with nearby aspartate residues are lost. In addition, the H2 polarization is unfavorable and the reduced side-chain volume may negatively affect the kinetics of the catalytic process.

Highlights

Hydrogen (H2) is among the most important energy carriers in a post-fossil era
We investigate the possible involvement of both neutral and positively charged R509 in the heterolytic splitting of H2 by E. coli Hyd-1, using QM/MM calculations with various sizes of QM regions
R509 is not expected to be directly involved in the reaction mechanism of the H2 activation by EH1. We propose this residue to be important for H2 activation by guiding its access to the active site, promoting its binding to nickel and facilitating its polarization

Summary

Introduction

Hydrogen (H2) is among the most important energy carriers in a post-fossil era. The generation of H2 as a biofuel from sustainable sources is a versatile alternative to the standard generation process from electrolysis of water which requires elevated temperature and expensive catalyst metals (Holladay et al, 2009; Rodionova et al, 2017). Shell of the hydrogenase enzyme: (i) an electronic function by polarizing the substrate H2, and (ii) a structural role by strong electrostatic interactions with negatively charged aspartate amino acid residues and displaying reduced conformational flexibility.

Results

Conclusion