Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D03345 (beta-Galactosidase)
 434 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lexA41 (formerly tsl-1) mutant was isolated as an ultraviolet light-resistant, temperature-sensitive derivative of its ultraviolet light-sensitive lexA3(Ind-) parent. Cells exhibit a so-called "split-phenotype", a phenomenon in which only a subset of the SOS responses can be detected physiologically following inducing treatments. lexA41 has been cloned and sequenced; the mutant gene retains the lexA3 mutation (Gly to Asp at position 85) and has a second mutation, lexA41 (Ala to Thr at position 131). We show that LexA41 protein is not cleaved by the RecA protein-catalyzed pathway in vivo, but the mutant protein is degraded by the Lon protease at both 32 degrees C and 42 degrees C. beta-Galactosidase activities of lac fusions to 13 different SOS promoters were measured at 30 degrees C and 42 degrees C to determine levels of expression and were found to vary considerably. The temperature-sensitive phenotype is a result of increased expression of sulA, which encodes a division inhibitor, at 42 degrees C. Excision repair genes, including uvrA, uvrB and uvrD, are constitutively expressed at 30 degrees C accounting for the ultraviolet light resistance of the lexA41 mutant, but the SOS mutagenesis operon, umuD,C, is not adequately derepressed, thereby explaining the failure to induce mutagenesis in this background. This differential expression of SOS genes gives a plausible explanation of the split-phenotype associated with lexA41.
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PMID:Differential repression of SOS genes by unstable lexA41 (tsl-1) protein causes a "split-phenotype" in Escherichia coli K-12. 310 14

Scant data exist on intracellular events during aminoglycoside-induced postantibiotic effect (PAE). We examined DNA, RNA, and protein syntheses after tobramycin exposure using [3H]thymidine, [14C]uracil, and [14C]alanine incorporation in a clinical Escherichia coli strain. Late-log-phase bacteria in oxygenated minimal salts medium at 37 degrees C were exposed to tobramycin (7.5 micrograms/ml) (twice the MIC) for 30 min. Tobramycin caused a kill of 2 log10 CFU/ml prior to drug removal by filtration and a 5-h PAE, measured by viable counts. Excess amounts of labelled precursors were added to tobramycin-exposed organisms during, immediately after, and at various intervals following exposure. In the presence of tobramycin, DNA, RNA, and protein syntheses were sequentially inhibited within 1 generation time. Following drug removal, both DNA and RNA syntheses promptly resumed, suggesting readily dissociable nonspecific binding to DNA and RNA. However, total protein synthesis did not resume until 4 h later. beta-Galactosidase activity, a measure of functional enzymatic protein synthesis, was also inhibited for 4 h after drug removal. Bacterium length, measured by confocal microscopy, increased during PAE. Two distinct populations eventually emerged: one that returned to control dimensions and one that remained excessively elongated by the end of PAE (2.5 microns versus 4.0 microns; P < 0.05). We hypothesize that only viable cells return to the control morphology. Flow cytometry showed enhanced DNA complexity during PAE, consistent with either impaired cellular protein synthesis in viable cells or perturbations in dying cells. In summary, duration of PAE correlated with inhibition of total and functional protein synthesis but not DNA or RNA synthesis.
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PMID:Correlation of tobramycin-induced inhibition of protein synthesis with postantibiotic effect in Escherichia coli. 750 45

The Escherichia coli rhaSR operon encodes two AraC family transcription activators, RhaS and RhaR, and is activated by RhaR in the presence of L-rhamnose. beta-Galactosidase assays of various rhaS-lacZ promoter fusions combined with mobility shift assays indicated that a cyclic AMP receptor protein (CRP) site located at -111.5 is also required for full activation of rhaSR expression. To address the mechanisms of activation by CRP and the RNA polymerase alpha-subunit C-terminal domain (alpha-CTD) at rhaSR, we tested the effects of alanine substitutions in CRP activating regions 1 and 2, overexpression of a truncated version of alpha (alpha-Delta235), and alanine substitutions throughout alpha-CTD. We found that DNA-contacting residues in alpha-CTD are required for full activation, and for simplicity, we discuss alpha-CTD as a third activator of rhaSR. CRP and RhaR could each partially activate transcription in the absence of the other two activators, and alpha-CTD was not capable of activation alone. In the case of CRP, this suggests that this activation involves neither an alpha-CTD interaction nor cooperative binding with RhaR, while in the case of RhaR, this suggests the likelihood of direct interactions with core RNA polymerase. We also found that CRP, RhaR, and alpha-CTD each have synergistic effects on activation by the others, suggesting direct or indirect interactions among all three. We have some evidence that the alpha-CTD-CRP and alpha-CTD-RhaR interactions might be direct. The magnitude of the synergistic effects was usually greater with just two activators than with all three, suggesting possible redundancies in the mechanisms of activation by CRP, alpha-CTD, and RhaR.
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PMID:Interdependence of activation at rhaSR by cyclic AMP receptor protein, the RNA polymerase alpha subunit C-terminal domain, and rhaR. 1107 23