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Partial Saturation of Menaquinone in Mycobacterium tuberculosis: Function and Essentiality of a Novel Reductase, MenJ
[Image: see text] Menaquinone (MK) with partially saturated isoprenyl moieties is found in a wide range of eubacteria and Archaea. In many Gram-positive organisms, including mycobacteria, it is the double bond found in the β-isoprene unit that is reduced. Mass spectral characterization of menaquinon...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582327/ https://www.ncbi.nlm.nih.gov/pubmed/26436137 http://dx.doi.org/10.1021/acscentsci.5b00212 |
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author | Upadhyay, Ashutosh Fontes, Fabio L. Gonzalez-Juarrero, Mercedes McNeil, Michael R. Crans, Debbie C. Jackson, Mary Crick, Dean C. |
author_facet | Upadhyay, Ashutosh Fontes, Fabio L. Gonzalez-Juarrero, Mercedes McNeil, Michael R. Crans, Debbie C. Jackson, Mary Crick, Dean C. |
author_sort | Upadhyay, Ashutosh |
collection | PubMed |
description | [Image: see text] Menaquinone (MK) with partially saturated isoprenyl moieties is found in a wide range of eubacteria and Archaea. In many Gram-positive organisms, including mycobacteria, it is the double bond found in the β-isoprene unit that is reduced. Mass spectral characterization of menaquinone from mycobacterial knockout strains and heterologous expression hosts demonstrates that Rv0561c (designated menJ) encodes an enzyme which reduces the β-isoprene unit of menaquinone in Mycobacterium tuberculosis, forming the predominant form of menaquinone found in mycobacteria. MenJ is highly conserved in mycobacteria species but is not required for growth in culture. Disruption of menJ reduces mycobacterial electron transport efficiency by 3-fold, but mycobacteria are able to maintain ATP levels by increasing the levels of the total menaquinone in the membrane; however, MenJ is required for M. tuberculosis survival in host macrophages. Thus, MK with partially hydrogenated isoprenyl moieties represents a novel virulence factor and MenJ is a contextually essential enzyme and a potential drug target in pathogenic mycobacteria and other Gram-positive pathogens. |
format | Online Article Text |
id | pubmed-4582327 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-45823272015-10-01 Partial Saturation of Menaquinone in Mycobacterium tuberculosis: Function and Essentiality of a Novel Reductase, MenJ Upadhyay, Ashutosh Fontes, Fabio L. Gonzalez-Juarrero, Mercedes McNeil, Michael R. Crans, Debbie C. Jackson, Mary Crick, Dean C. ACS Cent Sci [Image: see text] Menaquinone (MK) with partially saturated isoprenyl moieties is found in a wide range of eubacteria and Archaea. In many Gram-positive organisms, including mycobacteria, it is the double bond found in the β-isoprene unit that is reduced. Mass spectral characterization of menaquinone from mycobacterial knockout strains and heterologous expression hosts demonstrates that Rv0561c (designated menJ) encodes an enzyme which reduces the β-isoprene unit of menaquinone in Mycobacterium tuberculosis, forming the predominant form of menaquinone found in mycobacteria. MenJ is highly conserved in mycobacteria species but is not required for growth in culture. Disruption of menJ reduces mycobacterial electron transport efficiency by 3-fold, but mycobacteria are able to maintain ATP levels by increasing the levels of the total menaquinone in the membrane; however, MenJ is required for M. tuberculosis survival in host macrophages. Thus, MK with partially hydrogenated isoprenyl moieties represents a novel virulence factor and MenJ is a contextually essential enzyme and a potential drug target in pathogenic mycobacteria and other Gram-positive pathogens. American Chemical Society 2015-08-12 2015-09-23 /pmc/articles/PMC4582327/ /pubmed/26436137 http://dx.doi.org/10.1021/acscentsci.5b00212 Text en Copyright © 2015 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Upadhyay, Ashutosh Fontes, Fabio L. Gonzalez-Juarrero, Mercedes McNeil, Michael R. Crans, Debbie C. Jackson, Mary Crick, Dean C. Partial Saturation of Menaquinone in Mycobacterium tuberculosis: Function and Essentiality of a Novel Reductase, MenJ |
title | Partial Saturation of Menaquinone in Mycobacterium
tuberculosis: Function and Essentiality of a Novel Reductase,
MenJ |
title_full | Partial Saturation of Menaquinone in Mycobacterium
tuberculosis: Function and Essentiality of a Novel Reductase,
MenJ |
title_fullStr | Partial Saturation of Menaquinone in Mycobacterium
tuberculosis: Function and Essentiality of a Novel Reductase,
MenJ |
title_full_unstemmed | Partial Saturation of Menaquinone in Mycobacterium
tuberculosis: Function and Essentiality of a Novel Reductase,
MenJ |
title_short | Partial Saturation of Menaquinone in Mycobacterium
tuberculosis: Function and Essentiality of a Novel Reductase,
MenJ |
title_sort | partial saturation of menaquinone in mycobacterium
tuberculosis: function and essentiality of a novel reductase,
menj |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582327/ https://www.ncbi.nlm.nih.gov/pubmed/26436137 http://dx.doi.org/10.1021/acscentsci.5b00212 |
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