Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysyl-tRNA synthetase [L-lys:tRNAlys ligase (AMP forming) EC:6.1.1.6] has been purified to homogeneity from Mycobacterium smegmatis SN2. The enzyme is a dimer of molecular weight 126,000 and is composed of identical subunits. A detailed analysis of the kinetic mechanism of the lysyl-tRNA synthetase has been carried out. A rapid equilibrium random ter ter mechanism is proposed based on initial velocity and product inhibition studies. There is no evidence for the formation of enzyme-bound lysyl-adenylate. The reverse reaction, studied by the deacylation of lysyl-tRNA, requires the presence of both AMP and PPi. This observation is consistent with the mechanism proposed.
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PMID:Purification and kinetic mechanism of lysyl-tRNA synthetase from Mycobacterium smegmatis SN2. 385 66

The presence of 1-methyl adenine in transfer RNA is a feature that Mycobacterium smegmatis shares with only a few other prokaryotes. The enzyme 1-methyl adenine tRNA methyl transferase from this source has been purified and the preliminary results show the presence of two activity peaks with different substrate specificity.
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PMID:Studies on 1-methyl adenine transfer RNA methyltransferase of Mycobacterium smegmatis. 608 52

The nucleotide sequence of initiator tRNA from Mycobacterium smegmatis was determined to be pCGCGGGGUGGAGCAGCUCGGDAGCUCGCUGGGCUCAUAACCCAGAGm7GUCG CAGGU psi CGm1AAUCCUGUCCCCGCUACCAOH . The nucleotide sequence of Mycobacterium initiator tRNA was found to be the same as that of Streptomyces initiator tRNA, except that G46 and A57 were replaced by m7G46 and G57 , respectively. The striking feature of Mycobacterium initiator tRNA is the absence of ribothymidine at residue 54, and the presence of 1-methyladenosine at residue 58 which makes the sequence of this tRNA similar to that of eukaryotic initiator tRNA.
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PMID:Nucleotide sequence of initiator tRNA from Mycobacterium smegmatis. 672 83

Isoleucyl-tRNA synthetase has been purified to homogeneity from Mycobacterium smegmatis. The influence of spermine on the kinetics of valyl-tRNA and isoleucyl-tRNA formation has been investigated by Cleland's method (Cleland, W.W. (1963) Biochim. Biophys. Acta 67, 104-137, 173-187, 188-196). The results suggest that in the presence of spermine and suboptimal concentration of Mg2+, the formation of valyl-tRNA and isoleucyl-tRNA follows a sequential mechanism. In the presence of an optimal concentration of Mg2+, both valyl-tRNA and isoleucyl-tRNA formation proceeds by a ping-pong mechanism. However, in the presence of spermine and optimal concentrations of Mg2+, valyl-tRNA formation follows the ping-pong mechanism while isoleucyl-tRNA formation follows the sequential mechanism.
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PMID:Mechanism of aminoacylation of tRNA. Influence of spermine on the kinetics of aminoacyl-tRNA synthetases by isoleucyl- and valyl-tRNA synthetases from Mycobacterium smegmatis. 691 73

Recombinant bacteriophages provide efficient delivery systems for introducing reporter genes into specific bacterial hosts. We have constructed mycobacteriophage L5 recombinants carrying the firefly luciferase gene inserted into the tRNA region of the phage genome. Infection of Mycobacterium smegmatis by these phages results in expression of the luciferase gene and light emission. Fortuitously, the luciferase gene is expressed continuously in lysogens surviving infection. Synthesis of luciferase from a mycobacterial promoter created by cloning enables the detection of extremely small numbers of M. smegmatis cells. These reporter phages can be used to discriminate between drug-sensitive and drug-resistant strains of M. smegmatis, and may provide tools for the rapid identification and classification of antimycobacterial agents.
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PMID:L5 luciferase reporter mycobacteriophages: a sensitive tool for the detection and assay of live mycobacteria. 762 62

The 23S rDNA sequences of Mycobacterium paratuberculosis, M. avium and M. phlei and the sequences of the spacer regions between the 16S and 23S rRNA genes were determined. The overall 23S rDNA sequence identity between M. paratuberculosis and M. avium was 99.7% (nine mismatches), showing the very close relatedness of these mycobacteria. Evolutionary distances between the five known mycobacterial 23S rRNA/rDNA sequences and those of other Gram-positive G + C-rich bacteria were determined. The 23S rDNA sequences of mycobacteria showed two inserted regions compared to the other bacteria. A mycobacterial unique region contained one mismatch between M. paratuberculosis and M. avium. An Actinomycetales-specific insertion, consisting of 111 nucleotides, was completely identical for M. paratuberculosis and M. avium. The sequence of the intergenic spacer region between 16S and 23S rDNA had a length of 278 bp for M. paratuberculosis and M. avium with only two mismatches. The spacer region of the fast-growing M. phlei was 85 bp longer. No tRNA-encoding region was found in the spacer region.
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PMID:Comparison of the 23S ribosomal RNA genes and the spacer region between the 16S and 23S rRNA genes of the closely related Mycobacterium avium and Mycobacterium paratuberculosis and the fast-growing Mycobacterium phlei. 802 76

We have studied the base-pairing between the 3'-terminal CCA motif of a tRNA precursor and RNase P RNA by a phylogenetic mutational comparative approach. Thus, various derivatives of the Escherichia coli tRNA(Ser)Su1 precursor harboring all possible substitutions at either the first or the second C of the 3'-terminal CCA motif were generated. Cleavage site selection on these precursors was studied using mutant variants of M1 RNA, the catalytic subunit of E. coli RNase P, carrying changes at positions 292 or 293, which are involved in the interaction with the 3'-terminal CCA motif. From our data we conclude that these two C's in the substrate interact with the well-conserved G292 and G293 through canonical Watson-Crick base-pairing. Cleavage performed using reconstituted holoenzyme complexes suggests that this interaction also occurs in the presence of the C5 protein. Furthermore, we studied the interaction using various derivatives of RNase P RNAs from Mycoplasma hyopneumoniae and Mycobacterium tuberculosis. Our results suggest that the base-pairing between the 3'-terminal CCA motif and RNase P is present also in other bacterial RNase P-substrate complexes and is not limited to a particular bacterial species.
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PMID:Phylogenetic comparative mutational analysis of the base-pairing between RNase P RNA and its substrate. 866 13

We report here the cloning and primary structure of Mycobacterium tuberculosis isoleucyl-tRNA synthetase. The predicted 1035-amino acid protein is significantly more similar in sequence to eukaryote cytoplasmic than to other eubacterial isoleucyl-tRNA synthetases. This similarity correlates with the enzyme being resistant to pseudomonic acid A, a potent inhibitor of Escherichia coli and other eubacterial isoleucyl-tRNA synthetases, but not of eukaryote cytoplasmic enzymes. Consistent with its eukaryote-like features, and unlike E. coli isoleucyl-tRNA synthetase, the M. tuberculosis enzyme charged yeast isoleucine tRNA. In spite of these eukaryote-like features, M. tuberculosis isoleucyl-tRNA synthetase exhibited highly specific cross-species aminoacylation, as demonstrated by its ability to complement isoleucyl-tRNA synthetase-deficient mutants of E. coli. When introduced into a pseudomonic acid-sensitive wild-type strain of E. coli, the M. tuberculosis enzyme conferred trans-dominant resistance to the drug. The results demonstrate that the sequence of a tRNA synthetase could have predictive value with respect to the interaction of that synthetase with a specific inhibitor. The results also demonstrate that mobilization of a pathogen's gene for a drug-resistant protein target can spread resistance to other, normally drug-sensitive pathogens infecting the same host.
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PMID:A eubacterial Mycobacterium tuberculosis tRNA synthetase is eukaryote-like and resistant to a eubacterial-specific antisynthetase drug. 875 61

A continuous 75627 bp segment of the Mycobacterium leprae chromosome spanning the oriC region was sequenced. The gene order at this locus was similar to that found in the replication origin region of many other prokaryotes, particularly Mycobacterium tuberculosis and Streptomyces coelicolor. As in the case of several Gram-positive bacteria, essential genes involved in basic cellular functions, such as DNA or RNA metabolism (dnaA, dnaB, dnaN, gyrB, gyrA, pcnB, recF, rnpA, ssb), cell wall synthesis (ponA, pbpA) and probably cell division (gidB, rodA) were found. Strikingly, the gidA gene was absent from this part of the genome and there was no rRNA operon near oriC. The gyrA gene harbours an intein coding sequence indicating that protein splicing is required to produce the mature A subunit of DNA gyrase. Among the many other noteworthy features were ORFs encoding putative serine/threonine protein kinases and a protein phosphatase, three tRNA genes, one M. leprae-specific repetitive element and a glnQ pseudogene.
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PMID:Gene arrangement and organization in a approximately 76 kb fragment encompassing the oriC region of the chromosome of Mycobacterium leprae. 896 12

In spite of variations in the sequences of tRNAs, the genetic code (anticodon trinucleotides) is conserved in evolution. However, non-anticodon nucleotides which are species specific are known to prevent a given tRNA from functioning in all organisms. Conversely, species-specific tRNA contact residues in synthetases should also prevent cross-species acylation in a predictable way. To address this question, we investigated the relatively small tyrosine tRNA synthetase where contacts of Escherichia coli tRNA(Tyr) with the alpha2 dimeric protein have been localized by others to four specific sequence clusters on the three-dimensional structure of the Bacillus stearothermophilus enzyme. We used specific functional tests with a previously not-sequenced and not-characterized Mycobacterium tuberculosis enzyme and showed that it demonstrates species-specific aminoacylation in vivo and in vitro. The specificity observed fits exactly with the presence of the clusters characteristic of those established as important for recognition of E. coli tRNA. Conversely, we noted that a recent analysis of the tyrosine enzyme from the eukaryote pathogen Pneumocystis carinii showed just the opposite species specificity of tRNA recognition. According to our alignments, the sequences of the clusters diverge substantially from those seen with the M. tuberculosis, B. stearothermophilus and other enzymes. Thus, the presence or absence of species-specific residues in tRNA synthetases correlates in both directions with cross-species aminoacylation phenotypes, without reference to the associated tRNA sequences. We suggest that this kind of analysis can identify those synthetase-tRNA covariations which are needed to preserve the genetic code. These co-variations might be exploited to develop novel antibiotics against pathogens such as M. tuberculosis and P. carinii.
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PMID:Species-specific tRNA recognition in relation to tRNA synthetase contact residues. 919 96


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