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- Brännvall, Mathias, et al.
(författare)
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Metal ion cooperativity in ribozyme cleavage of RNA
- 2001
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424 .- 1091-6490. ; 98:23, s. 12943-12947
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Tidskriftsartikel (refereegranskat)abstract
- Combinations of chemical and genetic approaches were used to study the function of divalent metal ions in cleavage of RNA by the ribozyme RNase P RNA. We show that different divalent metal ions have differential effects on cleavage site recognition and rescue of cleavage activity by mixing divalent metal ions that do not promote cleavage by themselves. We conclude that efficient and correct cleavage is the result of cooperativity between divalent metal ions bound at different sites in the RNase P RNA-substrate complex. Complementation of a mutant RNase P RNA phenotype as a result of divalent metal ion replacement is demonstrated also. This finding together with other data indicate that one of the metal ions involved in this cooperativity is positioned near the cleavage site. The possibility that the Mg2+/Ca2+ ratio might regulate the activity of biocatalysts that depend on RNA for activity is discussed.
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| 7. |
- Herrmann, Björn, et al.
(författare)
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Characterization of the rnpB gene and the RNase P RNA in the order of Chlamydiales
- 2000
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Ingår i: International Journal of Systematic and Evolutionary Microbiology. - 1466-5026 .- 1466-5034. ; 50:Part 1, s. 149-158
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Tidskriftsartikel (refereegranskat)abstract
- The sequence of the RNase P RNA gene (rnpB) was determined for 60 strains representing all nine species in the family Chlamydiaceae and for the related Chlamydiales species, Parachlamydia acanthamoebae and Simkania negevensis. These sequences were used to infer evolutionary relationships among the Chlamydiaceae. The analysis separated Chlamydophila and Chlamydia into two lineages, with Chlamydophila forming three distinct clusters: the Chlamydophila pneumoniae strains; the Chlamydophila pecorum strains; and a third cluster comprising the species Chlamydophila psittaci, Chlamydophila abortus, Chlamydophila caviae and Chlamydophila felis. The Chlamydia line of descent contained two clusters, with the Chlamydia suis strains distinctly separated from strains of Chlamydia trachomatis and Chlamydia muridarum. This analysis indicated that the rnpB sequence and structure are distinctive markers for species in the Chlamydiaceae. It was also demonstrated that the RNase P RNA derived from Chlamydia trachomatis is able to cleave a tRNA precursor in the absence of protein. These findings are discussed in relation to the structure of Chlamydia RNase P RNA.
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| 8. |
- Kirsebom, Leif A., et al.
(författare)
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A method for detection of pathogenic organisms
- 2001
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Patent (populärvet., debatt m.m.)abstract
- The present invention relates to a method for detection of pathogenic organisms wherein the method includes differentiation between species. The method is especially suitable to detect and to diagnose infection by pathogenic organisms which are hard and/or laborious to detect with conventional methods. The method relies upon analysis of specific variable regions of the RNase P RNA gene, namely the P3 and/or P19 region(s).
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| 9. |
- Kirsebom, Leif A., et al.
(författare)
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METHOD AND KIT FOR DETECTION OF NOVEL PATHOGEN INHIBITORS
- 2001
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Patent (populärvet., debatt m.m.)abstract
- The present invention relates to a method for detection of novel pathogen inhibitors using models of pathogen specific, and metal binding structures/domains representing essential cellular molecules. The method enables identification of inhibitors that bind to any specific RNA molecule or protein that are essential for cell growth, proliferation and differentiation. The invention also relates to a kit for use in the method.Furthermore, the invention relates to use of aminoglycosides in the development of new drugs.
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| 10. |
- Kirsebom, Leif A.
(författare)
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RNase P RNA-mediated catalysis.
- 2002
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Ingår i: Biochemical Society Transactions. - 0300-5127 .- 1470-8752. ; 30:6, s. 1153-1158
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The endoribonuclease RNase P is involved in the processing of tRNA precursors to generate mature 5' termini. The catalytic activity of RNase P is associated with an RNA, RNase P RNA. A specific interaction between the 3' end of the substrate and RNase P RNA, to form an RNase P RNA-substrate complex, is referred to as the '73-294-interaction'. This interaction has an important role for efficient and correct cleavage to occur. Here our understanding of the contribution of the 73-294-interaction and metal ions, with respect to efficient and correct cleavage in RNase P RNA-mediated catalysis, will be discussed.
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| 12. |
- Kirsebom, Leif, et al.
(författare)
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Inhibition of RNase P processing
- 2001
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Ingår i: RNA-Binding Antibiotics. - : Eurekah.com, Austin, TX, USA and Landes Bioscences, Georgetown, TX, USA. ; , s. 56-72
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Mikkelsen, Nils E, et al.
(författare)
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Aminoglycoside binding displaces a divalent metal ion in a tRNA-neomycin B complex
- 2001
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Ingår i: Nature Structural Biology. - : Springer Science and Business Media LLC. - 1072-8368. ; 8:6, s. 510-514
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Tidskriftsartikel (refereegranskat)abstract
- Aminoglycosides bind to RNA and interfere with its function, and it has been suggested that aminoglycoside binding to RNA displaces essential divalent metal ions. Here we demonstrate that addition of various aminoglycosides inhibited Pb2+-induced cleavage of yeast tRNA(Phe). Cocrystallization of yeast tRNA(Phe) and an aminoglycoside, neomycin B, resulted in crystals that diffracted to 2.6 A and the structure of the complex was solved by molecular replacement. The structure shows that the neomycin B binding site overlaps with known divalent metal ion binding sites in yeast tRNA(Phe), providing direct evidence for the hypothesis that aminoglycosides displace metal ions. Additionally, the neomycin B binding site overlaps with major determinants for Escherichia coli phenylalanyl-tRNA-synthetase. Here we present data demonstrating that addition of neomycin B inhibited aminoacylation of E. coli tRNA(Phe) in the mid microM range. Given that aminoglycoside and metal ion binding sites overlap, we discuss that aminoglycosides can be considered as 'metal mimics'.
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| 15. |
- Ren, Yan-Guo, et al.
(författare)
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Inhibition of Klenow DNA polymerase and poly(A)-specific ribonuclease by aminoglycosides
- 2002
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Ingår i: RNA. - 1355-8382 .- 1469-9001. ; 8:11, s. 1393-1400
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Tidskriftsartikel (refereegranskat)abstract
- Aminoglycosides are known to bind and perturb the function of catalytic RNA. Here we show that they also are potent inhibitors of protein-based catalysis using Escherichia coli Klenow polymerase (pol) and mammalian poly(A)-specific ribonuclease (PARN) as model enzymes. The inhibition was pH dependent and released in a competitive manner by Mg2+. Kinetic analysis showed that neomycin B behaved as a mixed noncompetitive inhibitor. Iron-mediated hydroxyl radical cleavage was used to show that neomycin B interfered with metal-ion binding in the active sites of both enzymes. Our analysis suggests a mechanism of inhibition where the aminoglycoside binds in the active site of the enzyme and thereby displaces catalytically important divalent metal ions. The potential causes of aminoglycoside toxicity and the usage of aminoglycosides to probe, characterize, and perturb metalloenzymes are discussed.
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