Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction of representative beta-lactam antibiotics with a bacterial enzyme target has been mapped in three dimensions using X-ray diffraction data to 2.25 A resolution. Examination of complexes of cephalosporin C, benzylmonobactam, and alpha-(2,3)-methylenepenicillin G with the D-alanyl-D-alanine transpeptidase-carboxypeptidase from Streptomyces R61 shows that the enzyme's reactive serine has acylated the beta-lactam ring of each inhibitor. The known half-lives of the three acyl complexes can be correlated with the distance of the drug's carboxylate (or sulfonate) group from complementary groups on the DD-peptidase.
J Mol Graph 1989 Jun
PMID:Studying enzyme-beta-lactam interactions using X-ray diffraction. 248 68

Oligonucleotides that correspond to regions of the penicillin-binding protein 2 gene (penA) that differ between penicillin-sensitive and penicillin-resistant strains have been used as probes to classify the penA genes in a collection of penicillin-resistant gonococci isolated in Britain. 44/47 of those gonococcal strains that had minimal inhibitory concentrations of greater than or equal to 0.25 microgram benzylpenicillin per ml contained extensively altered penA genes which appeared to be very similar (or identical) to one or other of the two classes of altered penA genes that have been described previously. Since these two classes of altered penA genes are related, it appears that the great majority of the altered penA genes on non-beta-lactamase-producing penicillin-resistant gonococci have a clonal origin. The other three penicillin-resistant strains had altered penA genes that were different to those described previously. A crucial step in the development of the altered forms of PBP2 with decreased affinity for penicillin appears to have been the insertion of an extra codon within the transpeptidase domain of the penA gene. This insertion was found in the penA gene of all gonococci with minimal inhibitory concentrations of greater than 0.016 microgram benzylpenicillin per ml but was not found in any strains with minimal inhibitory concentrations of less than or equal to 0.016 microgram per ml.
Mol Microbiol 1989 Jan
PMID:Penicillin-binding protein 2 genes of non-beta-lactamase-producing, penicillin-resistant strains of Neisseria gonorrhoeae. 249 97

Antibodies to individual chloroplast ribosomal (r-)proteins of Chlamydomonas reinhardtii synthesized in either the chloroplast or the cytoplasm were used to examine the relatedness of Chlamydomonas r-proteins to r-proteins from the spinach (Spinacia oleracea) chloroplast, Escherichia coli, and the cyanobacterium Anabaena 7120. In addition, 35S-labeled chloroplast r-proteins from large and small subunits of C. reinhardtii were co-electrophoresed on 2-D gels with unlabeled r-proteins from similar subunits of spinach chloroplasts, E. coli, and Anabaena to compare their size and net charge. Comigrating protein pairs were not always immunologically related, whereas immunologically related r-protein pairs often did not comigrate but differed only slightly in charge and molecular weight. In contrast, when 35S-labeled chloroplast r-proteins from large and small subunits of a closely related species C. smithii were coelectrophoresed with unlabeled C. reinhardtii chloroplast r-proteins, only one pair of proteins from each subunit showed a net displacement in mobility. Analysis of immunoblots of one-dimensional SDS and two-dimensional urea/SDS gels of large and small subunit r-proteins from these species revealed more antigenic conservation among the four species of large subunit r-proteins than small subunit r-proteins. Anabaena r-proteins showed the greatest immunological similarity to C. reinhardtii chloroplast r-proteins. In general, antisera made against chloroplast-synthesized r-proteins in C. reinhardtii showed much higher levels of cross-reactivity with r-proteins from Anabaena, spinach, and E. coli than did antisera to cytoplasmically synthesized r-proteins. All spinach r-proteins that cross-reacted with antisera to chloroplast-synthesized r-proteins of C. reinhardtii are known to be made in the chloroplast (Dorne et al. 1984b). Four E. coli r-proteins encoded by the S10 operon (L2, S3, L16, and L23) were found to be conserved immunologically among the four species. Two of the large subunit r-proteins, L2 and L16, are essential for peptidyltransferase activity. The third (L23) and two other E. coli large subunit r-proteins (L5 and L27) that have immunological equivalents among the four species are functionally related to but not essential for peptidyltransferase activity.
J Mol Evol 1989 Jul
PMID:Electrophoretic and immunological comparisons of chloroplast and prokaryotic ribosomal proteins reveal that certain families of large subunit proteins are evolutionarily conserved. 250 32

Clinical isolates of Streptococcus pneumoniae that have greatly increased levels of resistance to penicillin (greater than 1000-fold) have been reported from South Africa during the last ten years. Penicillin resistance in these strains is entirely due to the development of penicillin-binding proteins (PBPs) with decreased affinity for penicillin. We have cloned and sequenced the coding region for the transpeptidase domain of penicillin-binding protein 2B from three penicillin-sensitive strains of S. pneumoniae and from a penicillin-resistant South African strain. The amino acid sequences of the transpeptidase domains of PBP2B of the three penicillin-sensitive strains were identical and there were only between one and four differences in the nucleotide sequences of their coding regions. The corresponding region of the PBP2B gene from the penicillin-resistant strain differed by 74 nucleotide substitutions which resulted in 17 alterations in the amino acid sequence of PBP2B. The most remarkable alteration that has occurred during the development of the 'penicillin-resistant' form of PBP2B is the substitution of seven consecutive residues in a region that is predicted to form a loop at the bottom of the penicillin-binding site.
Mol Microbiol 1989 Jan
PMID:Extensive re-modelling of the transpeptidase domain of penicillin-binding protein 2B of a penicillin-resistant South African isolate of Streptococcus pneumoniae. 265 41

Using the same system that we used in a previous study [Eur. J. Biochem. 164:53-58 (1987)], we have further examined the kinetics of inhibition of peptide bond formation by chloramphenicol in the puromycin reaction and we have applied conditions that are known to cause conformational changes to the 70 S ribosome. These conditions are the change in reaction temperature from 25 degrees to 5 degrees and the change in the concentration of NH4+ ion (50 mM versus 100 mM). The initial transient phase of competitive inhibition is now (100 mM NH4+ and 5 degrees or 50 mM NH4+ and 25 degrees) much more pronounced than at 100 mM NH4+ and 25 degrees. Simple competitive inhibition is the only type of inhibition we can find when analyzing the kinetic information given by the initial slopes of the first-order time plots. This contrasts with the kinetics observed at 100 mM NH4+ and 25 degrees, where a transient phase of competitive inhibition is followed (at higher concentrations of chloramphenicol) by a phase of mixed noncompetitive inhibition, which corresponds to a lower kcat for peptidyltransferase (EC 2.3.2.12). This pattern of inhibition (competitive-mixed noncompetitive) was again obtained in this study using a ribosomal complex [acetyl[3H]Phe-tRNA-poly(U)-ribosome] of low peptidyltransferase activity (kcat = 0.91 min-1), as was obtained previously when we used a complex of high activity (kcat = 2.00 min-1). Thus, the lowering of the kcat of peptidyltransferase induced by chloramphenicol (from 0.91 to 0.34 min-1) can occur irrespective of the activity status of peptidyltransferase. The conformational changes that are induced by chloramphenicol and lead to the lowering of the kcat of peptidyltransferase need both relatively high (100 mM) concentrations of monovalent ion and higher temperature (25 degrees as opposed to 5 degrees). If these conditions are not met, the inhibition is simple competitive and the kcat of peptidyltransferase remains unchanged. These results offer an explanation as to why a clear-cut competitive inhibition of the puromycin reaction by chloramphenicol has been difficult to observe for so many years.
Mol Pharmacol 1989 Oct
PMID:Type of inhibition of peptide bond formation by chloramphenicol depends on the temperature and the concentration of ammonium ions. 268 5

Focal proliferative and neoplastic lung lesions induced in Syrian hamsters by dihydroxy-di-n-propylnitrosamine (DHPN) were investigated using a combined histochemical, autoradiographic and electron microscopic approach. Expression of elevated glucose-6-phosphate dehydrogenase (G6PD) and gammaglutamyl-transpeptidase (GGT) activities and levels of immunohistochemically demonstrable glutathione S-transferase placental form (GST-P) were evident in epithelial cells of focal proliferative populations and bronchioloalveolar neoplasms. Binding for the GST-C form, normally only weak, became very pronounced in the stromal elements of DHPN-induced lesions. Increased labelling with tritiated thymidine was associated with increase in morphological atypia within the tumours. Although the enzyme phenotype findings were equivocal the presence of lamellar bodies in some cells of focal proliferative and neoplastic lesions suggested an origin from alveolar type II cells. The present results regarding changed enzyme phenotype in lung lesions suggest important similarities at the biochemical level for the process of neoplasia in the different target organs of DHPN in the hamster and indicate that GST-P may be a useful 'marker' for lung neoplasia.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Altered enzyme expression in propylnitrosamine-induced Syrian hamster lung lesions. 288 90

CheZ is the product of one of six genes required for sensory processing in Escherichia coli and Salmonella typhimurium chemotaxis. This 24-kDa cytoplasmic protein is modified by a posttranslational methylation reaction. The modified residue has been identified by analysis of radioactively labeled protein from two-dimensional electrophoretograms and Edman degradation of CheZ protein isolated by immunoaffinity chromatography using anti-CheZ monoclonal antibodies. The methylated group is an N-monomethylmethionine residue at the amino terminus of CheZ. L16, a ribosomal protein that is required for peptidyltransferase activity during protein synthesis, is also methylated at its amino-terminal methionine (Chen, R., Brosius, J., and Wittmann-Liebold, B. (1977) J. Mol. Biol. 111, 173-181). Homologous sequences at the amino termini of L16 and CheZ raise the possibility that a single S-adenosylmethionine-dependent methyltransferase modifies both proteins.
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PMID:A second type of protein methylation reaction in bacterial chemotaxis. 329 25

The effects of the administration of tryptophan and/or cysteine on carbon tetrachloride (CCl4)-induced hepatic injury were investigated. Rats received CCl4 (1 ml/kg ip) followed 6 hr later by tryptophan (300 mg/kg) and/or cysteine (950 mg/kg) via stomach tube and rats were killed after 24 hr. Treatment with tryptophan, cysteine, or both reduced the degree of hepatic necrosis observed histologically. While CCl4 caused polyribosomal disaggregation and decreased [14C]leucine incorporation into liver proteins in vitro and in vivo, treatment with tryptophan, cysteine, or both caused a shift in polyribosomes toward heavier aggregation and protein synthesis was increased. Serum activities of lactic dehydrogenase (LDH), glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and gamma-glutamyl-transpeptidase were markedly increased after CCl4 alone but after subsequent treatment with cysteine or with tryptophan and cysteine appreciable decreases occurred. Glutathione concentration decreased but total amount remained constant in the livers of CCl4-treated rats while subsequent treatment with cysteine alone or together with tryptophan elevated both levels of glutathione. Using isolated hepatocytes, CCl4 caused decreases in cell viability, in release of LDH, and in [14C]leucine incorporation into protein. Treatment with CCl4 and tryptophan and/or cysteine revealed that cysteine alone or with tryptophan improved cell viability and decreased LDH release of the cells, while tryptophan alone or with cysteine improved protein synthesis. Upon cytologic evaluation, the isolated hepatocytes revealed membrane distortions after CCl4 alone but these were less marked after CCl4 plus tryptophan, cysteine, or both (most improvement). Thus, tryptophan and cysteine act in a beneficial manner against CCl4-induced hepatic injury in the rat.
Exp Mol Pathol 1985 Dec
PMID:Protective effect of tryptophan and cysteine against carbon tetrachloride-induced liver injury. 406 14

Two mutants lacking protein L15 from the ribosome as determined by two dimensional gels were investigated using a number of different immunological methods. One strain was found to possess several protein L15 moieties which differed in net charge and in size. The other showed no evidence of L15 cross-reacting material (CRM) on the ribosome or in the supernatant. Ribosomes of this strain were used as a control in the process of the localisation of protein L15 on the surface of the large subunit of Escherichia coli ribosomes. Antigenic determinants mapped in the angle between the central protuberance and the L1 protuberance. Protein L15 has been assigned a central role in the large subunit in vitro assembly map, in peptidyltransferase activity and in the binding of erythromycin, so the significance of a mutant lacking this protein is discussed.
Mol Gen Genet 1983
PMID:Characterisation of a mutant from Escherichia coli lacking protein L15 and localisation of protein L15 by immuno-electron microscopy. 619 16

Stoichiometric amounts of ribosomal proteins and RNA derived from the 50S subunit reconstitute to fully active particles under the conditions of a two-step incubation procedure. After the first incubation, all components are found in a particle that is activated in the second incubation [Dohme, F. & Nierhaus, K. H. (1976) J. Mol. Biol. 107, 585-599]. Here we describe the assembly dependences of the ribosomal components in the first incubation. Assembly dependence is the requirements of one protein that, before it binds, another must be first built into the ribosome. After incubation of 23S RNA and the proteins under observation, the mixture was subjected to sucrose gradient analysis. The RNA-protein complex was precipitated with trichloroacetic acid and the proteins were identified by NaDodSO4 gel electrophoresis. The assembly dependences of 26 proteins could be elucidated. In a second series of experiments, the incorporation of 3H-labeled 5S RNA in the 23S-protein complex was analyzed. It was found that L5, L15, and L18 are absolutely required for 5S RNA incorporation. In addition, two of the three proteins L2, L3, and L4 are needed, in excellent agreement with the protein dependences. The data are summarized in an assembly map. Comparison with other data shows a structural domain at the 5' end of 23S RNA around protein L20 combining all proteins essential in the early assembly. All the proteins essential for the reconstitution of the peptidyltransferase protein form a skeleton of strong assembly dependences. Finally, L proteins whose genes are present in large transcriptional units on the chromosome depend on each other during assembly.
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PMID:Assembly map of the large subunit (50S) of Escherichia coli ribosomes. 703 83


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