Characterization of Dual Substrate Binding Sites in the Homodimeric Structure of Escherichia coli mRNA Interferase MazF

Li, Guang Yao; Zhang, Yonglong; Chan, Mitchell C.Y.; Mal, Tapas K.; Hoeflich, Klaus P.; Inouye, Masayori; Ikura, Mitsuhiko

doi:10.1016/j.jmb.2005.12.035

Cited by 52 publications

(62 citation statements)

References 33 publications

(38 reference statements)

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“…the MazF dimer (when the S3-S4 loop 2 of one MazF monomer interacts with the H1 helix of the other) could also directly interact with the hydrophobic moieties of the RNA substrate (29). This would also be consistent with the sequence relationships shown in our alignment, since residues comprising these two regions are conserved among the three UACAU-cleaving MazF toxins but distinct from E. coli MazF.…”

Section: Figsupporting

confidence: 82%

“…7). Curiously, although nuclear magnetic resonance studies by Li et al implicate E. coli MazF H28 in substrate recognition (29), which is consistent with its solvent exposure in the X-ray crystal structure of the MazE-MazF complex (24), there are no histidines at or near this position in the three UACAU-cleaving MazF toxins (Fig. 7).…”

Section: Fig 2 Expression Of Mazf-cd Inhibits Growth and Maze-cd Prevmentioning

confidence: 56%

“…7). It is possible that the position of the histidine influences substrate specificity, as proposed by Li et al (29). However, they also proposed that the relatively hydrophobic site formed by the binding site created in…”

Section: Fig 2 Expression Of Mazf-cd Inhibits Growth and Maze-cd Prevmentioning

confidence: 97%

“…7). In other MazF orthologs without a histidine at position 28, there is one in proximity that is instead proposed to contribute to substrate recognition (e.g., H17 of Kid and H23 of ChpBK) (29). However, the three UACAU-cleaving MazF toxins have an absolutely conserved histidine (H63 in MazF-cd) that is predicted as the first residue of ␤-sheet S4 immediately following loop 2 (Fig.…”

Section: Fig 2 Expression Of Mazf-cd Inhibits Growth and Maze-cd Prevmentioning

confidence: 99%

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Clostridium difficile MazF Toxin Exhibits Selective, Not Global, mRNA Cleavage

et al. 2012

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e Clostridium difficile is an important, emerging nosocomial pathogen. The transition from harmless colonization to disease is typically preceded by antimicrobial therapy, which alters the balance of the intestinal flora, enabling C. difficile to proliferate in the colon. One of the most perplexing aspects of the C. difficile infectious cycle is its ability to survive antimicrobial therapy and transition from inert colonization to active infection. Toxin-antitoxin (TA) systems have been implicated in facilitating persistence after antibiotic treatment. We identified only one TA system in C. difficile strain 630 (epidemic type X), designated MazE-cd and MazF-cd, a counterpart of the well-characterized Escherichia coli MazEF TA system. This E. coli MazF toxin cleaves mRNA at ACA sequences, leading to global mRNA degradation, growth arrest, and death. Likewise, MazF-cd expression in E. coli or Clostridium perfringens resulted in growth arrest. Primer extension analysis revealed that MazF-cd cleaved RNA at the five-base consensus sequence UACAU, suggesting that the mRNAs susceptible to cleavage comprise a subset of total mRNAs. In agreement, we observed differential cleavage of several mRNAs by MazF-cd in vivo, revealing a direct correlation between the number of cleavage recognition sites within a given transcript and its susceptibility to degradation by MazF-cd. Interestingly, upon detailed statistical analyses of the C. difficile transcriptome, the major C. difficile virulence factor toxin B (TcdB) and CwpV, a cell wall protein involved in aggregation, were predicted to be significantly resistant to MazF-cd cleavage.

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Section: Figsupporting

confidence: 82%

Section: Fig 2 Expression Of Mazf-cd Inhibits Growth and Maze-cd Prevmentioning

confidence: 56%

Section: Fig 2 Expression Of Mazf-cd Inhibits Growth and Maze-cd Prevmentioning

confidence: 97%

Section: Fig 2 Expression Of Mazf-cd Inhibits Growth and Maze-cd Prevmentioning

confidence: 99%

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Clostridium difficile MazF Toxin Exhibits Selective, Not Global, mRNA Cleavage

et al. 2012

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“…3B). However, the exact stoichiometry by which the C-terminal arm of MazE Sa mimics the similarly charged sugarphosphate backbone of RNA to inhibit MazF Sa toxin activity by occupying the RNA binding site on the MazF Sa toxin as described for E. coli (19) will require further detailed crystal structure studies of the MazE/MazF Sa complex.…”

Section: Discussionmentioning

confidence: 99%

Characterization of MazF _Sa , an Endoribonuclease from Staphylococcus aureus

Donegan

Memmi

et al. 2007

J Bacteriol

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The mazEF homologs of Staphylococcus aureus, designated mazEF sa , have been shown to cotranscribe with the sigB operon under stress conditions. In this study, we showed that MazEF Sa , as with their Escherichia coli counterparts, compose a toxin-antitoxin module wherein MazF Sa leads to rapid cell growth arrest and loss in viable CFU upon overexpression. MazF Sa is a novel sequence-specific endoribonuclease which cleaves mRNA to inhibit protein synthesis. Using ctpA mRNA as the model substrate both in vitro and in vivo, we demonstrated that MazF Sa cleaves single-strand RNA preferentially at the 5 side of the first U or 3 side of the second U residue within the consensus sequences VUUV (where V and V are A, C, or G and may or may not be identical). Binding studies confirmed that the antitoxin MazE Sa binds MazF Sa to form a complex to inhibit the endoribonuclease activity of MazF Sa . Contrary to the system in E. coli, exposure to selected antibiotics augmented mazEF sa transcription, akin to what one would anticipate from the environmental stress response of the sigB system. These data indicate that the mazEF system of S. aureus differs from the gram-negative counterparts with respect to mRNA cleavage specificity and antibiotic stresses.

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Cost implications of new treatments for advanced colorectal cancer

Wong

Meropol

Speier

et al. 2009

Cancer

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A new tricyanate ester monomer of a tris(4‐hydroxyphenyl)benzene derivative was synthesized in 6‐steps with a 63% overall yield. The geminal substitution of phenyl rings on ethane, in addition to the creation of a racemic/diastereomeric mixture, resulted in a liquid monomer whereas compounds with similar structure and symmetry have melting points typically over 100 °C. Key properties of the polycyanurate, such as the glass transition temperature and moisture resistance, were positively influenced by the higher crosslink density provided by the monomer. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010

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Characterization of Dual Substrate Binding Sites in the Homodimeric Structure of Escherichia coli mRNA Interferase MazF

Cited by 52 publications

References 33 publications

Clostridium difficile MazF Toxin Exhibits Selective, Not Global, mRNA Cleavage

Clostridium difficile MazF Toxin Exhibits Selective, Not Global, mRNA Cleavage

Characterization of MazF _Sa , an Endoribonuclease from Staphylococcus aureus

Cost implications of new treatments for advanced colorectal cancer

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Characterization of Dual Substrate Binding Sites in the Homodimeric Structure of Escherichia coli mRNA Interferase MazF

Cited by 52 publications

References 33 publications

Clostridium difficile MazF Toxin Exhibits Selective, Not Global, mRNA Cleavage

Clostridium difficile MazF Toxin Exhibits Selective, Not Global, mRNA Cleavage

Characterization of MazF Sa , an Endoribonuclease from Staphylococcus aureus

Cost implications of new treatments for advanced colorectal cancer

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Product

Resources

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Characterization of MazF _Sa , an Endoribonuclease from Staphylococcus aureus