Unraveling the Reaction Mechanism of Mo/Cu CO Dehydrogenase Using QM/MM Calculations
Ritacca, Alessandra G. ; Rovaletti, Anna ; Moro, Giorgio ; Cosentino, Ugo ; Ryde, Ulf LU
; Sicilia, Emilia
and Greco, Claudio
LU
(2022)
In ACS Catalysis
12(12).
p.7336-7343
- Abstract
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... (More)
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.
(Less)
- author
- Ritacca, Alessandra G.
; Rovaletti, Anna
; Moro, Giorgio
; Cosentino, Ugo
; Ryde, Ulf
LU
; Sicilia, Emilia
and Greco, Claudio
LU
- organization
- publishing date
- 2022-06
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- BigQM, biocatalysis, CO oxidation, dehydrogenase, molybdenum, O resistance, QM/MM, xanthine oxidase
- in
- ACS Catalysis
- volume
- 12
- issue
- 12
- pages
- 8 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- scopus:85144669022
- ISSN
- 2155-5435
- DOI
- 10.1021/acscatal.2c01408
- language
- English
- LU publication?
- yes
- id
- 8088cb0f-12f2-4223-95d6-0a5590fdc036
- date added to LUP
- 2023-01-12 16:03:08
- date last changed
- 2023-04-07 20:42:31
@article{8088cb0f-12f2-4223-95d6-0a5590fdc036,
abstract = {{<p>Some microorganisms, like the aerobic soil bacteria, Oligotropha carboxidovorans, have the capability to oxidize the highly toxic atmospheric gas carbon monoxide (CO) into CO<sub>2</sub> 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 CO<sub>2</sub> 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 CO<sub>2</sub> by Mo/Cu CO dehydrogenase. Surprisingly, we found that the detachment of CO<sub>2</sub> 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.</p>}},
author = {{Ritacca, Alessandra G. and Rovaletti, Anna and Moro, Giorgio and Cosentino, Ugo and Ryde, Ulf and Sicilia, Emilia and Greco, Claudio}},
issn = {{2155-5435}},
keywords = {{BigQM; biocatalysis; CO oxidation; dehydrogenase; molybdenum; O resistance; QM/MM; xanthine oxidase}},
language = {{eng}},
number = {{12}},
pages = {{7336--7343}},
publisher = {{The American Chemical Society (ACS)}},
series = {{ACS Catalysis}},
title = {{Unraveling the Reaction Mechanism of Mo/Cu CO Dehydrogenase Using QM/MM Calculations}},
url = {{http://dx.doi.org/10.1021/acscatal.2c01408}},
doi = {{10.1021/acscatal.2c01408}},
volume = {{12}},
year = {{2022}},
}