Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ribosomal protein L3 (L3) has been demonstrated to participate in formation of the peptidyltransferase center and is essential for its catalytic activity. In the present study we show that L3 is able to bind nucleotide triphosphates with high and specific affinity in vitro. L3 was serendipitously identified by screening of a genomic phage library from a primitive kinetoplastid flagellate Trypanoplasma borreli with the ATPase domain of the topoisomerase II gene as a probe. The cloned gene was overexpressed and purified as a his-tag fusion protein in E. coli. Radioligand binding experiments, using [gamma-35S]ATP, showed that L3 is able to bind ATP but also GTP and UTP with similar high affinity (IC50 50-100 nM), while it has no ATPase activity. Furthermore, we showed that L3 has more than 500-fold higher affinity for nucleotide triphosphates compared to the corresponding nucleotide monophosphates and diphosphates. Molecular genetic and biochemical analyses allowed us to localize the NTP binding domain of L3 to the N-terminal 296 residues. Suramin, a polysulfonated naphthylamine derivative of urea, known for its chemotherapeutic effects completely inhibited the binding of [gamma-35S]ATP at subclinical levels. Results obtained with surface plasmon resonance technology showed that suramin both forms weak multimolecular complexes with L3 and binds strongly to L3 in nearly stoichiometric amounts.
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PMID:Suramin blocks nucleotide triphosphate binding to ribosomal protein L3 from Trypanoplasma borreli. 1071 4

We report the emergence of a multidrug-resistant Haemophilus influenzae strain in a patient with common variable immunodeficiency suffering from recurrent bronchopneumonia caused by H. influenzae. After the patient had received several antibiotic therapies, a strain was isolated showing resistance to ampicillin, ampicillin/sulbactam, cefazolin, cefuroxime, ciprofloxacin, and clarithromycin. Polymerase chain reaction analyses and sequencing revealed the presence of the beta-lactamase gene bla(TEM-1), two mutations (A502T and R517H) in the ftsI gene encoding the transpeptidase region of the penicillin-binding protein 3, and one mutation in the ribosomal protein gene L4 (G65D) conferring resistance to beta-lactams and macrolides, respectively. Additionally, the plasmid-encoded aac(6')-Ib-cr gene mediating slightly reduced susceptibility to quinolones and two mutations in the DNA gyrase gene gyrA and one mutation in the topoisomerase IV gene parC were identified leading to a high-level fluoroquinolone-resistant phenotype. In conclusion, the treatment of H. influenzae infections accompanied by high bacterial loads such as bronchopneumonia can be complicated by the selection of multidrug-resistant strains. Moreover, the emergence of aac(6')-Ib-cr in H. influenzae causing low fluoroquinolone resistance levels might have contributed to the selection of DNA gyrase and topoisomerase IV mutants.
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PMID:Emergence of a multidrug-resistant Haemophilus influenzae strain causing chronic pneumonia in a patient with common variable immunodeficiency. 2309 85