Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.41 (isocitrate dehydrogenase)
 3,101 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

NAD+-specific isocitrate dehydrogenase (IDH) has been reported to bind sequences in 5'-untranslated regions of yeast mitochondrial mRNAs. In the current study, an RNA transcript containing the 5'-untranslated region of the mRNA from the yeast mitochondrial COX2 gene is shown to be an allosteric inhibitor of the affinity-purified yeast enzyme. At 0.1 microM concentrations of the transcript, velocity of the IDH reaction is reduced to 20% of the value obtained in the absence of the RNA transcript. This inhibition is due to a 2. 5-fold increase in the S0.5 value for isocitrate. Significant inhibition of IDH activity is also obtained with a transcript containing a portion of the 5'-untranslated region of the yeast mitochondrial ATP9 gene and with an antisense form of the COX2 transcript, both of which contain potential stem-loop secondary structures implicated in binding of IDH. In contrast, much higher concentrations of yeast tRNA or poly(A)mRNA, respectively, 33- and 60-fold greater than that required for the COX2 transcript, are required to produce a 50% decrease in velocity. These results suggest that inhibition of activity is relatively specific for the 5'-untranslated regions of mitochondrial mRNAs. All measurable inhibition of IDH activity by RNA is eliminated by addition of 100 microM concentrations of the allosteric activator AMP. At equivalent concentrations, dAMP is less efficient than AMP as an allosteric activator of IDH and is proportionally less effective in protecting against inhibition of activity by the COX2 transcript. Other nucleotides that are not allosteric activators fail to protect IDH activity from inhibitory effects of RNA. Thus, alleviation of catalytic inhibition of IDH by mitochondrial mRNA correlates with the property of allosteric activation.
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PMID:Allosteric inhibition of NAD+-specific isocitrate dehydrogenase by a mitochondrial mRNA. 1080 12

A class of gyrase mutants of Salmonella enterica mimics the properties of bacteria exposed to quinolones. These mutants suffer spontaneous DNA breakage during normal growth and depend on recombinational repair for viability. Unlike quinolone-treated bacteria, however, they do not show accumulation of cleavable gyrase-DNA complexes. In recA or recB mutant backgrounds, the temperature-sensitive (ts) allele gyrA208 causes rapid cell death at 43 degrees. Here, we isolated "suppressor-of-death" mutations, that is, secondary changes that allow a gyrA208 recB double mutant to survive a prolonged exposure to 43 degrees and subsequently to form colonies at 28 degrees. In most isolates, the secondary change was itself a ts mutation. Three ts alleles were mapped in genes coding for amino acyl tRNA synthetases (alaS, glnS, and lysS). Allele alaS216 completely abolished DNA breakage in a gyrA208 recA double mutant. Likewise, treating this mutant with chloramphenicol prevented death and DNA damage at 43 degrees. Additional suppressors of gyrA208 lethality include rpoB mutations and, surprisingly, icd mutations inactivating isocitrate dehydrogenase. We postulate that the primary effect of the gyrase alteration is to hamper replication fork movement. Inhibiting DNA replication under conditions of continuing macromolecular synthesis ("unbalanced growth") activates a mechanism that causes DNA breakage and cell death, reminiscent of "thymineless" lethality.
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PMID:Growth-dependent DNA breakage and cell death in a gyrase mutant of Salmonella. 1177 84

To obtain a global insight into the dynamic protein expression pattern in Pichia stipitis during xylose fermentation in the presence of three representative inhibitors (acetic acid, vanillin and 5-hydroxymethylfurfural), proteins were extracted for quantitative proteomic analysis using 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) on a liquid chromatography-mass/mass spectrometry instrument. Interestingly, aconitase (Aco1p) and NAD-isocitrate dehydrogenase (Idh1p) were upregulated during the middle exponential phase in the presence of the three inhibitors during tricarboxylic acid cycle. We speculated that yeast cells adaptively increased the expression of the tricarboxylic acid cycle proteins to compensate for low NADH derived from glycolysis in the presence of the three inhibitors. Proteins related to amino acid metabolism, aminoacyl tRNA synthesis and stress response were also significantly affected in the presence of the three inhibitors. Taken together, quantitative proteomic analysis is capable of monitoring P. stipitis xylose fermentation under inhibitor conditions and identifying physiological changes, such as stress response.
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PMID:Quantitative proteomic analysis of xylose fermentation strain Pichia stipitis CBS 5776 to lignocellulosic inhibitors acetic acid, vanillin and 5-hydroxymethylfurfural. 3029 76