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TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification
Lack of molybdenum cofactor (Moco) in Escherichia coli leads to hypersensitivity to the mutagenic and toxic effects of N-hydroxylated base analogs, such as 6-N-hydroxylaminopurine (HAP). This phenotype is due to the loss of two Moco-dependent activities, YcbX and YiiM, that are capable of reducing H...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831636/ https://www.ncbi.nlm.nih.gov/pubmed/23894086 http://dx.doi.org/10.1002/mbo3.108 |
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author | Kozmin, Stanislav G Stepchenkova, Elena I Schaaper, Roel M |
author_facet | Kozmin, Stanislav G Stepchenkova, Elena I Schaaper, Roel M |
author_sort | Kozmin, Stanislav G |
collection | PubMed |
description | Lack of molybdenum cofactor (Moco) in Escherichia coli leads to hypersensitivity to the mutagenic and toxic effects of N-hydroxylated base analogs, such as 6-N-hydroxylaminopurine (HAP). This phenotype is due to the loss of two Moco-dependent activities, YcbX and YiiM, that are capable of reducing HAP to adenine. Here, we describe two novel HAP-sensitive mutants containing a defect in iscS or tusA (yhhP) gene. IscS is a major L-cysteine desulfurase involved in iron–sulfur cluster synthesis, thiamine synthesis, and tRNA thiomodification. TusA is a small sulfur-carrier protein that interacts with IscS. We show that both IscS and TusA operate within the Moco-dependent pathway. Like other Moco-deficient strains, tusA and iscS mutants are HAP sensitive and resistant to chlorate under anaerobic conditions. The base-analog sensitivity of iscS or tusA strains could be suppressed by supplying exogenous L-cysteine or sulfide or by an increase in endogenous sulfur donors (cysB constitutive mutant). The data suggest that iscS and tusA mutants have a defect in the mobilization of sulfur required for active YcbX/YiiM proteins as well as nitrate reductase, presumably due to lack of functional Moco. Overall, our data imply a novel and indispensable role of the IscS/TusA complex in the activity of several molybdoenzymes. |
format | Online Article Text |
id | pubmed-3831636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-38316362013-11-29 TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification Kozmin, Stanislav G Stepchenkova, Elena I Schaaper, Roel M Microbiologyopen Original Research Lack of molybdenum cofactor (Moco) in Escherichia coli leads to hypersensitivity to the mutagenic and toxic effects of N-hydroxylated base analogs, such as 6-N-hydroxylaminopurine (HAP). This phenotype is due to the loss of two Moco-dependent activities, YcbX and YiiM, that are capable of reducing HAP to adenine. Here, we describe two novel HAP-sensitive mutants containing a defect in iscS or tusA (yhhP) gene. IscS is a major L-cysteine desulfurase involved in iron–sulfur cluster synthesis, thiamine synthesis, and tRNA thiomodification. TusA is a small sulfur-carrier protein that interacts with IscS. We show that both IscS and TusA operate within the Moco-dependent pathway. Like other Moco-deficient strains, tusA and iscS mutants are HAP sensitive and resistant to chlorate under anaerobic conditions. The base-analog sensitivity of iscS or tusA strains could be suppressed by supplying exogenous L-cysteine or sulfide or by an increase in endogenous sulfur donors (cysB constitutive mutant). The data suggest that iscS and tusA mutants have a defect in the mobilization of sulfur required for active YcbX/YiiM proteins as well as nitrate reductase, presumably due to lack of functional Moco. Overall, our data imply a novel and indispensable role of the IscS/TusA complex in the activity of several molybdoenzymes. Blackwell Publishing Ltd 2013-10 2013-07-29 /pmc/articles/PMC3831636/ /pubmed/23894086 http://dx.doi.org/10.1002/mbo3.108 Text en © 2013 Published by John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Original Research Kozmin, Stanislav G Stepchenkova, Elena I Schaaper, Roel M TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification |
title | TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification |
title_full | TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification |
title_fullStr | TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification |
title_full_unstemmed | TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification |
title_short | TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification |
title_sort | tusa (yhhp) and iscs are required for molybdenum cofactor-dependent base-analog detoxification |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3831636/ https://www.ncbi.nlm.nih.gov/pubmed/23894086 http://dx.doi.org/10.1002/mbo3.108 |
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