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Keywords = tri-hemic enzyme

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18 pages, 2664 KiB  
Article
Coordination of the N-Terminal Heme in the Non-Classical Peroxidase from Escherichia coli
by Ricardo N. S. Oliveira, Sara R. M. M. de Aguiar and Sofia R. Pauleta
Molecules 2023, 28(12), 4598; https://doi.org/10.3390/molecules28124598 - 7 Jun 2023
Viewed by 2177
Abstract
The non-classical bacterial peroxidase from Escherichia coli, YhjA, is proposed to deal with peroxidative stress in the periplasm when the bacterium is exposed to anoxic environments, defending it from hydrogen peroxide and allowing it to thrive under those conditions. This enzyme has [...] Read more.
The non-classical bacterial peroxidase from Escherichia coli, YhjA, is proposed to deal with peroxidative stress in the periplasm when the bacterium is exposed to anoxic environments, defending it from hydrogen peroxide and allowing it to thrive under those conditions. This enzyme has a predicted transmembrane helix and is proposed to receive electrons from the quinol pool in an electron transfer pathway involving two hemes (NT and E) to accomplish the reduction of hydrogen peroxide in the periplasm at the third heme (P). Compared with classical bacterial peroxidases, these enzymes have an additional N-terminal domain binding the NT heme. In the absence of a structure of this protein, several residues (M82, M125 and H134) were mutated to identify the axial ligand of the NT heme. Spectroscopic data demonstrate differences only between the YhjA and YhjA M125A variant. In the YhjA M125A variant, the NT heme is high-spin with a lower reduction potential than in the wild-type. Thermostability was studied by circular dichroism, demonstrating that YhjA M125A is thermodynamically more unstable than YhjA, with a lower TM (43 °C vs. 50 °C). These data also corroborate the structural model of this enzyme. The axial ligand of the NT heme was validated to be M125, and mutation of this residue was proven to affect the spectroscopic, kinetic, and thermodynamic properties of YhjA. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
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20 pages, 3640 KiB  
Review
Recent Advances in Structural Studies of Cytochrome bd and Its Potential Application as a Drug Target
by Thorsten Friedrich, Daniel Wohlwend and Vitaliy B. Borisov
Int. J. Mol. Sci. 2022, 23(6), 3166; https://doi.org/10.3390/ijms23063166 - 15 Mar 2022
Cited by 34 | Viewed by 4993
Abstract
Cytochrome bd is a triheme copper-free terminal oxidase in membrane respiratory chains of prokaryotes. This unique molecular machine couples electron transfer from quinol to O2 with the generation of a proton motive force without proton pumping. Apart from energy conservation, the bd [...] Read more.
Cytochrome bd is a triheme copper-free terminal oxidase in membrane respiratory chains of prokaryotes. This unique molecular machine couples electron transfer from quinol to O2 with the generation of a proton motive force without proton pumping. Apart from energy conservation, the bd enzyme plays an additional key role in the microbial cell, being involved in the response to different environmental stressors. Cytochrome bd promotes virulence in a number of pathogenic species that makes it a suitable molecular drug target candidate. This review focuses on recent advances in understanding the structure of cytochrome bd and the development of its selective inhibitors. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Advances in Biochemistry)
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