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Photo Ulf Ryde

Ulf Ryde

Professor

Photo Ulf Ryde

Unraveling the Reaction Mechanism of Mo/Cu CO Dehydrogenase Using QM/MM Calculations

Author

  • Alessandra G. Ritacca
  • Anna Rovaletti
  • Giorgio Moro
  • Ugo Cosentino
  • Ulf Ryde
  • Emilia Sicilia
  • Claudio Greco

Summary, in English

Some microorganisms, like the aerobic soil bacteria, Oligotropha carboxidovorans, have the capability to oxidize the highly toxic atmospheric gas carbon monoxide (CO) into CO2 through CO dehydrogenase enzymes, whose active site contains a bimetallic MoCu center. Over the last decades, a number of experimental and theoretical investigations were devoted to understanding the mechanism of CO oxidation and, in particular, the role of a very stable thiocarbonate intermediate that may be formed during the catalytic cycle. The occurrence of such an intermediate was reported to make the CO2 release step kinetically difficult. In this work, by using an accurate QM/MM approach and energy refinement by means of the BigQM method, we were able to determine the role of such an intermediate and propose a novel mechanism for the oxidation of CO into CO2 by Mo/Cu CO dehydrogenase. Surprisingly, we found that the detachment of CO2 occurs directly from the product of the Mo=O nucleophilic attack reaction on the carbon of CO aided by the transient coordination of the active site glutamate to the Mo ion. The estimated activation barrier is in good agreement with the experimental one, while the thiocarbonate turned out to not interfere with the CO-oxidation catalytic cycle. The results highlight the importance of the environmental effects in the assembly of the molecular model and in the choice of the computational protocol. Our accurate modeling of the enzyme also allowed us to exclude the involvement of a frustrated Lewis pair in the CO-oxidation mechanism, which has recently been suggested based on an analysis of structural and electronic features of synthetic mimics of the Mo/Cu CO dehydrogenase active site.

Department/s

  • Computational Chemistry
  • eSSENCE: The e-Science Collaboration

Publishing year

2022-06

Language

English

Pages

7336-7343

Publication/Series

ACS Catalysis

Volume

12

Issue

12

Document type

Journal article

Publisher

The American Chemical Society (ACS)

Topic

  • Theoretical Chemistry (including Computational Chemistry)

Keywords

  • BigQM
  • biocatalysis
  • CO oxidation
  • dehydrogenase
  • molybdenum
  • O resistance
  • QM/MM
  • xanthine oxidase

Status

Published

ISBN/ISSN/Other

  • ISSN: 2155-5435