Mutations at nucleotides G2251 and U2585 of 23 S rRNA perturb the peptidyl transferase center of the ribosome

Green, Rachel; Samaha, Raymond R.; Noller, Harry F.

doi:10.1006/jmbi.1996.0780

Cited by 70 publications

(32 citation statements)

References 24 publications

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“…Alongside, the ribose rings of A2451 and C2452 fit into an angle created between the sugar and the base of the rotating A76, probably adding to the guidance provided by the rear wall ( Figure 4C). In the last stage (150-1798 of rotation) P-site contacts similar to those reported previously (Green et al, 1997;Bocchetta et al, 1998;Nissen et al, 2000;Yusupov et al, 2001) are formed. These include the base pair of C75 with G2251, the interactions of C2063, A2451 and U2585 with A76, and of A2062 with the rotated amino acid.…”

Section: The Rotatory Motionsupporting

confidence: 82%

Symmetry at the active site of the ribosome: structural and functional implications

Agmon

Bashan

Zarivach

et al. 2005

Biological Chemistry

115

167

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The sizable symmetrical region, comprising 180 ribosomal RNA nucleotides, which has been identified in and around the peptidyl transferase center (PTC) in crystal structures of eubacterial and archaeal large ribosomal subunits, indicates its universality, confirms that the ribosome is a ribozyme and evokes the suggestion that the PTC evolved by gene fusion. The symmetrical region can act as a center that coordinates amino acid polymerization by transferring intra-ribosomal signals between remote functional locations, as it connects, directly or through its extensions, the PTC, the three tRNA sites, the tunnel entrance, and the regions hosting elongation factors. Significant deviations from the overall symmetry stabilize the entire region and can be correlated with the shaping and guiding of the motion of the tRNA 39-end from the A-into the P-site. The linkage between the elaborate PTC architecture and the spatial arrangements of the tRNA 39-ends revealed the rotatory mechanism that integrates peptide bond formation, translocation within the PTC and nascent protein entrance into the exit tunnel. The positional catalysis exerted by the ribosome places the reactants in stereochemistry close to the intermediate state and facilitates the catalytic contribution of the P-site tRNA 29-hydroxyl.

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Section: The Rotatory Motionsupporting

confidence: 82%

Symmetry at the active site of the ribosome: structural and functional implications

Agmon

Bashan

Zarivach

et al. 2005

Biological Chemistry

115

167

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“…Recently, Asai et al (1999) reported a complete exchange of rRNA genes between different bacterial species and replacement of a 23S rRNA gene segment of E. coli by the corresponding region of yeast. If a transgressed rRNA gene or gene segment brings to the recipient a beneficial property, such as antibiotic resistance (Green et al, 1997 ;Mankin, 1997), it will be kept and may eventually replace the endogenous gene(s) via gene conversion (Hillis et al, 1990). High levels of localized intergenic base variations corresponding to the stem of a hairpin have also been reported (Ueda et al, 1999 ;.…”

Section: Discussionmentioning

confidence: 99%

Comparative sequence analyses reveal frequent occurrence of short segments containing an abnormally high number of non-random base variations in bacterial rRNA genes

Wang

Zhang

2000

Microbiology

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rRNA genes are thought unlikely to be laterally transferred, because rRNA must coevolve with a large number of cellular components to form the highly sophisticated translation apparatus and perform protein synthesis. In this paper, the authors first hypothesized that lateral gene transfer (LGT) might occur to rRNA genes via replacement of gene segments encoding individual domains of rRNA : the ' simplified complexity hypothesis '. Comparative sequence analyses of the 16S and 23S rRNA genes from a large number of actinomycete species frequently identified rRNA genes containing short segments with an abnormally high number of non-random base variations. These variations were nearly always characterized by complementing covariations of several paired bases within the stem of a hairpin. The nature of these base variations is not consistent with random mutations but satisfies well the predictions of the ' simplified complexity hypothesis '. The most parsimonious explanation for this phenomenon is the lateral transfer of rRNA gene segments between different bacterial species. This mode of LGT may create mosaic rRNA genes and occur repeatedly in different regions of a gene, gradually destroying the evolutionary history recorded in the nucleotide sequence.

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“…S3 d-f). The flexibility of U2585 is important for the induced fit of P-tRNA binding at the PTC (27) and the binding of tRNA mimics to the PTC is impaired by mutation of U2585 (28). Therefore, the nonproductive conformation of U2585 for peptide bond formation may contribute to the inhibitory action of linezolid, analogous to the effect ob- served when U2585 shifts upon streptogramin B binding at the PTC (Fig.…”

Section: Conformational Flexibility In U2585 Permits Different Oxazolmentioning

confidence: 99%

The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning

Wilson

Schluenzen

Harms

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

274

256

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The oxazolidinones represent the first new class of antibiotics to enter into clinical usage within the past 30 years, but their binding site and mechanism of action has not been fully characterized. We have determined the crystal structure of the oxazolidinone linezolid bound to the Deinococcus radiodurans 50S ribosomal subunit. Linezolid binds in the A site pocket at the peptidyltransferase center of the ribosome overlapping the aminoacyl moiety of an A-site bound tRNA as well as many clinically important antibiotics. Binding of linezolid stabilizes a distinct conformation of the universally conserved 23S rRNA nucleotide U2585 that would be nonproductive for peptide bond formation. In conjunction with available biochemical data, we present a model whereby oxazolidinones impart their inhibitory effect by perturbing the correct positioning of tRNAs on the ribosome.

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Mutations at nucleotides G2251 and U2585 of 23 S rRNA perturb the peptidyl transferase center of the ribosome

Cited by 70 publications

References 24 publications

Symmetry at the active site of the ribosome: structural and functional implications

Symmetry at the active site of the ribosome: structural and functional implications

Comparative sequence analyses reveal frequent occurrence of short segments containing an abnormally high number of non-random base variations in bacterial rRNA genes

The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning

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