TusA (YhhP) and IscS are required for molybdenum cofactor-dependent base-analog detoxification.

Abstract

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.

• Authors: Stanislav G Kozmin, Elena I Stepchenkova, Roel M Schaaper
• Journal: MicrobiologyOpen (Microbiologyopen) Vol. 2 Issue 5 Pg. 743-55 (Oct 2013) ISSN: 2045-8827 [Electronic] England
• PMID: 23894086 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2013 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Chemical References

• Chlorates
• Coenzymes
• Escherichia coli Proteins
• Metalloproteins
• Molybdenum Cofactors
• Mutagens
• Pteridines
• TusA protein, E coli
• 6-N-hydroxylaminopurine
• Sulfur
• molybdenum cofactor
• Carbon-Sulfur Lyases
• cysteine desulfurase
• Adenine
• Cysteine
• chloric acid

Topics

• Adenine (analogs & derivatives, pharmacology)
• Anaerobiosis
• Carbon-Sulfur Lyases (genetics, metabolism)
• Chlorates (pharmacology)
• Coenzymes (metabolism)
• Cysteine (metabolism, pharmacology)
• Escherichia coli (drug effects, genetics, metabolism)
• Escherichia coli Proteins (genetics, metabolism)
• Gene Expression Regulation, Bacterial
• Metalloproteins (metabolism)
• Molybdenum Cofactors
• Mutagens (pharmacology)
• Mutation
• Pteridines (metabolism)
• Signal Transduction
• Sulfur (metabolism)