MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kallia-Raftopoulos, S.
Right arrow Articles by Coutsogeorgopoulos, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kallia-Raftopoulos, S.
Right arrow Articles by Coutsogeorgopoulos, C.

New aspects of the kinetics of inhibition by lincomycin of peptide bond formation

S Kallia-Raftopoulos, DL Kalpaxis and C Coutsogeorgopoulos

Laboratory of Biochemistry, School of Medicine, University of Patras, Greece.

We have investigated the inhibition of peptide bond formation by the antibiotic lincomycin, at 150 mM NH4Cl. We have used an in vitro system in which a ribosomal ternary complex, the acetyl[3H] phenylalanine-tRNA- 70 S ribosome-poly(U) complex (complex C), reacts with puromycin, forming peptide bonds. Complex C can be considered an analog of the elongating ribosomal complex and puromycin an analog of aminoacyl-tRNA. In a previous study we reported on the kinetics of inhibition by lincomycin at 100 mM NH4Cl. In the present investigation, we find that an increase of the ammonium ion concentration to 150 mM causes profound changes in the kinetic behavior of the system, which can be summarized as follows. First, the association rate for complex C and lincomycin is increased. At a lincomycin concentration of 10 microM the apparent equilibration rate constant is 4.3 min-1 at 100 mM NH4Cl, whereas it becomes 6.7 min-1 at 150 mM. Second, at 150 mM NH4Cl, with increasing concentrations of lincomycin, there is a transition from competitive to mixed-noncompetitive inhibition. The prevailing notion is that lincomycin acts at the ribosomal A-site, a mechanism that agrees only with competitive kinetics (mutually exclusive binding between puromycin and lincomycin). At the molecular level, the change in the kinetics of inhibition that we observe may mean that the mutually exclusive binding between aminoacyl-tRNA and lincomycin is converted to simultaneous binding, as a result of conformational changes occurring in the elongating ribosomal complex.

Volume 46, Issue 5, pp. 1009-1014, 11/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
E. C. Kouvela, A. D. Petropoulos, and D. L. Kalpaxis
Unraveling New Features of Clindamycin Interaction with Functional Ribosomes and Dependence of the Drug Potency on Polyamines
J. Biol. Chem., August 11, 2006; 281(32): 23103 - 23110.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. Kallia-Raftopoulos and D. L. Kalpaxis
Slow Sequential Conformational Changes in Escherichia coli Ribosomes Induced by Lincomycin: Kinetic Evidence
Mol. Pharmacol., November 1, 1999; 56(5): 1042 - 1046.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1994 by the American Society for Pharmacology and Experimental Therapeutics