title: Molybdenum cofactor-dependent resistance to N-hydroxylated base analogs in Escherichia coli is independent of MobA function.
abstract: Lack of molybdenum cofactor (MoCo) in Escherichia coli and related microorganisms was found to cause hypersensitivity to certain N-hydroxylated base analogs, such as HAP (6-N-hydroxylaminopurine). This observation has lead to a previous proposal that E. coli contains a molybdoenzyme capable of detoxifying such N-hydroxylated analogs. Here, we show that, unexpectedly, deletion of all known or putative molybdoenzymes in E. coli failed to reveal any base-analog sensitivity, suggesting that a novel type of MoCo-dependent activity is involved. Further, we establish that protection against the analogs does not require the common molybdopterin guanine-dinucleotide (MGD) form of the cofactor, but instead the guanosine monophosphate (GMP)-free version of MoCo (MPT) is sufficient.
authors.affiliation: Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
authors.forename: Stanislav G
authors.initials: SG
authors.lastname: Kozmin
authors.forename: Roel M
authors.initials: RM
authors.lastname: Schaaper
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000633:toxicity; D003067:Coenzymes / Q000737:chemistry / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005798:Genes, Bacterial; D008667:Metalloproteins / Q000737:chemistry / Q000378:metabolism*; D000090006:Molybdenum Cofactors; D009153:Mutagens / Q000633:toxicity; D011621:Pteridines / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000225:Adenine; D003067:Coenzymes; D029968:Escherichia coli Proteins; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D009153:Mutagens; D011621:Pteridines; C095754:mobA protein, E coli; C032610:6-N-hydroxylaminopurine; C022261:molybdopterin