Linked Life Data

2843509

Source:http://linkedlifedata.com/resource/pubmed/id/2843509

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
1988-10-19
pubmed:abstractText
According to the allosteric three-site model for the ribosomal elongation cycle (Rheinberger, H.J. and Nierhaus, K.H. (1986) J. Biol. Chem. 261, 9133-9139), two types of A site (aminoacyl-tRNA site) occupation exist. First is the A site occupation after initiation (i-type), with only one site, the P site (peptidyl-tRNA site), being prefilled with a tRNA (initiator tRNA). Second is the A site occupation after an elongation cycle (e-type), with two prefilled sites, namely the P and E sites containing peptidyl-tRNA and deacylated tRNA, respectively. The individual reactions of the elongation cycle were tested, including both types of A site occupation in the presence of various antibiotics. A test system was used allowing the functional studies to be made with quantitative tRNA binding at 6 mM Mg2+. The following results were obtained: 1) thiostrepton (5 x 10(-6) M) induced a complete block of both EF-(elongation factor) G dependent and EF-G independent translocation, in agreement with older observations. The A-site occupation of the e-type was severely inhibited in contrast to that of the i-type. Thus, thiostrepton blocks the allosteric transitions in both directions, i.e. the transition from pre- to post-translocational state (translocation) and that from the post- to the pre-translocational state (A site occupation of the e-type). In addition the ribosomal binding of EF-G.[3H] GMPPNP was inhibited by about 60%. 2) Similarly, viomycin (5 x 10(-5) M) appears to be an inhibitor of both allosteric transitions, since it strongly inhibited the e-type (but not the i-type) A site occupation in addition to translocation. 3) The aminoglycosides streptomycin, hygromycin B, neomycin, kanamycin, and gentamicin prevented A site occupation of the e-type (residual activity below 15%). Neomycin and hygromycin, in addition, blocked the translocation reaction. Only marginal effects were observed with A site occupation of the i-type. It appears that the inhibition of the A site binding of the e-type (allosteric transition from the post- to the pretranslocational state) is the predominant effect of the misreading-inducing aminoglycosides.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Aminoglycosides, http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents, http://linkedlifedata.com/resource/pubmed/chemical/Galactosyltransferases, http://linkedlifedata.com/resource/pubmed/chemical/Guanylyl Imidodiphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Lincomycin, http://linkedlifedata.com/resource/pubmed/chemical/Magnesium, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Elongation Factor G, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Elongation Factors, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Transfer, Amino Acid-Specific, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Transfer, Phe, http://linkedlifedata.com/resource/pubmed/chemical/Thiostrepton, http://linkedlifedata.com/resource/pubmed/chemical/Viomycin
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
263
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13103-11
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
The allosteric three-site model for the ribosomal elongation cycle. New insights into the inhibition mechanisms of aminoglycosides, thiostrepton, and viomycin.
pubmed:affiliation
Max-Planck-Institut für Molekulare Genetik, Abteilung Wittmann, Berlin-Dahlem, West Germany.
pubmed:publicationType
Journal Article