ArticlePloS one2012
Structure-function relationships of the Mycobacterium tuberculosis transcription factor WhiB1.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- WhiB-like proteins: Diversity of structure, function and mechanism.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Structural insights into the functional divergence of WhiB-like proteins in Mycobacterium tuberculosis.Molecular cell · 2021Article
- Structural basis of non-canonical transcriptional regulation by the σA-bound iron-sulfur protein WhiB1 in M. tuberculosis.Nucleic acids research · 2020Article
- The actinobacterial WhiB-like (Wbl) family of transcription factors.Molecular microbiology · 2018Review
- Structure of a Wbl protein and implications for NO sensing by M. tuberculosis.Nature communications · 2017Article
- Comparative Analyses of Selection Operating on Nontranslated Intergenic Regions of Diverse Bacterial Species.Genetics · 2017Article
- Monitoring global protein thiol-oxidation and protein S-mycothiolation in Mycobacterium smegmatis under hypochlorite stress.Scientific reports · 2017Article
- Structure and function of HWE/HisKA2-family sensor histidine kinases.Current opinion in microbiology · 2017Review
- Article
- The Conserved Actinobacterial Two-Component System MtrAB Coordinates Chloramphenicol Production with Sporulation inFrontiers in microbiology · 2017Article
- WblAch, a pivotal activator of natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis L10, is positively regulated by AdpAch.Applied and environmental microbiology · 2014Article
- Insights into redox sensing metalloproteins in Mycobacterium tuberculosis.Journal of inorganic biochemistry · 2014Review
- Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide.Virulence · 2014Review
- The mycobacterial antibiotic resistance determinant WhiB7 acts as a transcriptional activator by binding the primary sigma factor SigA (RpoV).Nucleic acids research · 2013Article
- WhiB7, an Fe-S-dependent transcription factor that activates species-specific repertoires of drug resistance determinants in actinobacteria.The Journal of biological chemistry · 2013Article
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4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMembers of the WhiB-like (Wbl) protein family possess iron-sulfur clusters and are implicated in the regulation of developmental processes in Actinomycetes. Mycobacterium tuberculosis possesses seven Wbl proteins. The [4Fe-4S] cluster of M. tuberculosis WhiB1 is relatively insensitive to O(2) but very sensitive to nitric oxide (NO). Nitric oxide nitrosylates the WhiB1 iron-sulfur cluster and promotes DNA-binding; the apo-forms of WhiB1 also bind DNA. However, the molecular requirements for iron-sulfur cluster acquisition and for DNA-binding by WhiB1 are poorly characterized. METHODS AND
findingsWhiB1 variants were created by site-directed mutagenesis and the abilities of the corresponding proteins to acquire an iron-sulfur cluster and/or bind to whiB1 promoter DNA were assessed. All four Cys residues (Cys9, 37, 40, and 46) in the N-terminal region of WhiB1 were required for incorporation of a [4Fe-4S] cluster, whereas a possible alternative cluster ligand Asp13 (by analogy with M. smegmatis WhiB2) was not. The C-terminal region of WhiB1 is predicted to house the DNA-binding domain of the protein consisting of a predicted β-turn ((58)GVWGG(62)) followed by two amino acid motifs ((72)KRRN(75) and (78)TKAR(81)) that are conserved in WhiB1 proteins. Gly residues (Gly58, 61 and 62) in the β-turn and positively-charged residues (Lys72, Arg73, Arg74, Lys79 and Arg81) in the downstream conserved regions were required for binding of WhiB1 DNA.
conclusionsSite-directed mutagenesis of M. tuberculosis whiB1 and characterization of the corresponding proteins has been used to explore structure-function relationships of the NO-responsive transcription factor WhiB1. This showed that all four conserved Cys residues in the N-terminal region are required for incorporation of iron-sulfur clusters but not for DNA-binding. Analysis of variants with amino acid substitutions in the C-terminal region revealed the crucial roles played by a predicted β-turn and two conserved positively-charged motifs in facilitating DNA-binding, but not iron-sulfur cluster acquisition, by WhiB1.
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