@article {38556,
	title = {Unexpected abundance of coenzyme F(420)-dependent enzymes in Mycobacterium tuberculosis and other actinobacteria},
	journal = {Journal of bacteriologyJournal of bacteriology},
	volume = {192},
	year = {2010},
	note = {http://www.ncbi.nlm.nih.gov/pubmed/20675471?dopt=Abstract},
	type = {10.1128/JB.00425-10},
	abstract = {Regimens targeting Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), require long courses of treatment and a combination of three or more drugs. An increase in drug-resistant strains of M. tuberculosis demonstrates the need for additional TB-specific drugs. A notable feature of M. tuberculosis is coenzyme F(420), which is distributed sporadically and sparsely among prokaryotes. This distribution allows for comparative genomics-based investigations. Phylogenetic profiling (comparison of differential gene content) based on F(420) biosynthesis nominated many actinobacterial proteins as candidate F(420)-dependent enzymes. Three such families dominated the results: the luciferase-like monooxygenase (LLM), pyridoxamine 5{\textquoteright}-phosphate oxidase (PPOX), and deazaflavin-dependent nitroreductase (DDN) families. The DDN family was determined to be limited to F(420)-producing species. The LLM and PPOX families were observed in F(420)-producing species as well as species lacking F(420) but were particularly numerous in many actinobacterial species, including M. tuberculosis. Partitioning the LLM and PPOX families based on an organism{\textquoteright}s ability to make F(420) allowed the application of the SIMBAL (sites inferred by metabolic background assertion labeling) profiling method to identify F(420)-correlated subsequences. These regions were found to correspond to flavonoid cofactor binding sites. Significantly, these results showed that M. tuberculosis carries at least 28 separate F(420)-dependent enzymes, most of unknown function, and a paucity of flavin mononucleotide (FMN)-dependent proteins in these families. While prevalent in mycobacteria, markers of F(420) biosynthesis appeared to be absent from the normal human gut flora. These findings suggest that M. tuberculosis relies heavily on coenzyme F(420) for its redox reactions. This dependence and the cofactor{\textquoteright}s rarity may make F(420)-related proteins promising drug targets.},
	keywords = {Actinobacteria, Amino Acid Sequence, Binding Sites, Coenzymes, Flavonoids, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Genome, Bacterial, molecular biology, Molecular Sequence Data, Molecular Structure, Mycobacterium tuberculosis, Phylogeny, Protein Conformation, Riboflavin},
	author = {J. Selengut and Haft, Daniel H.}
}
@article {49778,
	title = {Unexpected abundance of coenzyme F(420)-dependent enzymes in Mycobacterium tuberculosis and other actinobacteria.},
	journal = {J Bacteriol},
	volume = {192},
	year = {2010},
	month = {2010 Nov},
	pages = {5788-98},
	abstract = {<p>Regimens targeting Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), require long courses of treatment and a combination of three or more drugs. An increase in drug-resistant strains of M. tuberculosis demonstrates the need for additional TB-specific drugs. A notable feature of M. tuberculosis is coenzyme F(420), which is distributed sporadically and sparsely among prokaryotes. This distribution allows for comparative genomics-based investigations. Phylogenetic profiling (comparison of differential gene content) based on F(420) biosynthesis nominated many actinobacterial proteins as candidate F(420)-dependent enzymes. Three such families dominated the results: the luciferase-like monooxygenase (LLM), pyridoxamine 5{\textquoteright}-phosphate oxidase (PPOX), and deazaflavin-dependent nitroreductase (DDN) families. The DDN family was determined to be limited to F(420)-producing species. The LLM and PPOX families were observed in F(420)-producing species as well as species lacking F(420) but were particularly numerous in many actinobacterial species, including M. tuberculosis. Partitioning the LLM and PPOX families based on an organism{\textquoteright}s ability to make F(420) allowed the application of the SIMBAL (sites inferred by metabolic background assertion labeling) profiling method to identify F(420)-correlated subsequences. These regions were found to correspond to flavonoid cofactor binding sites. Significantly, these results showed that M. tuberculosis carries at least 28 separate F(420)-dependent enzymes, most of unknown function, and a paucity of flavin mononucleotide (FMN)-dependent proteins in these families. While prevalent in mycobacteria, markers of F(420) biosynthesis appeared to be absent from the normal human gut flora. These findings suggest that M. tuberculosis relies heavily on coenzyme F(420) for its redox reactions. This dependence and the cofactor{\textquoteright}s rarity may make F(420)-related proteins promising drug targets.</p>},
	keywords = {Actinobacteria, Amino Acid Sequence, Binding Sites, Coenzymes, Flavonoids, Gene Expression Profiling, Gene Expression Regulation, Bacterial, Genome, Bacterial, molecular biology, Molecular Sequence Data, Molecular Structure, Mycobacterium tuberculosis, Phylogeny, Protein Conformation, Riboflavin},
	issn = {1098-5530},
	doi = {10.1128/JB.00425-10},
	author = {Selengut, Jeremy D and Haft, Daniel H}
}
@article {38536,
	title = {The transcription factor Eyes absent is a protein tyrosine phosphatase},
	journal = {NatureNature},
	volume = {426},
	year = {2003},
	note = {http://www.ncbi.nlm.nih.gov/pubmed/14628053?dopt=Abstract},
	type = {10.1038/nature02097},
	abstract = {Post-translational modifications provide sensitive and flexible mechanisms to dynamically modulate protein function in response to specific signalling inputs. In the case of transcription factors, changes in phosphorylation state can influence protein stability, conformation, subcellular localization, cofactor interactions, transactivation potential and transcriptional output. Here we show that the evolutionarily conserved transcription factor Eyes absent (Eya) belongs to the phosphatase subgroup of the haloacid dehalogenase (HAD) superfamily, and propose a function for it as a non-thiol-based protein tyrosine phosphatase. Experiments performed in cultured Drosophila cells and in vitro indicate that Eyes absent has intrinsic protein tyrosine phosphatase activity and can autocatalytically dephosphorylate itself. Confirming the biological significance of this function, mutations that disrupt the phosphatase active site severely compromise the ability of Eyes absent to promote eye specification and development in Drosophila. Given the functional importance of phosphorylation-dependent modulation of transcription factor activity, this evidence for a nuclear transcriptional coactivator with intrinsic phosphatase activity suggests an unanticipated method of fine-tuning transcriptional regulation.},
	keywords = {Amino Acid Motifs, Amino Acid Sequence, Animals, Antibodies, Phospho-Specific, Drosophila melanogaster, Drosophila Proteins, Embryonic Induction, eye, Eye Proteins, Gene Expression Regulation, Kinetics, Mice, Models, Molecular, Molecular Sequence Data, Mutation, Phosphorylation, Protein Conformation, Protein Tyrosine Phosphatases, Substrate Specificity, Transcription Factors},
	author = {Tootle, Tina L. and Silver, Serena J. and Davies, Erin L. and Newman, Victoria and Latek, Robert R. and Mills, Ishara A. and J. Selengut and Parlikar, Beth E. W. and Rebay, Ilaria}
}
