The structural basis of ribosome activity in peptide bond synthesis.

  title={The structural basis of ribosome activity in peptide bond synthesis.},
  author={Poul Nissen and Jeffrey L Hansen and Nenad Ban and Peter B Moore and Thomas A. Steitz},
  volume={289 5481},
Using the atomic structures of the large ribosomal subunit from Haloarcula marismortui and its complexes with two substrate analogs, we establish that the ribosome is a ribozyme and address the catalytic properties of its all-RNA active site. Both substrate analogs are contacted exclusively by conserved ribosomal RNA (rRNA) residues from domain V of 23S rRNA; there are no protein side-chain atoms closer than about 18 angstroms to the peptide bond being synthesized. The mechanism of peptide bond… 

Essential Mechanisms in the Catalysis of Peptide Bond Formation on the Ribosome*

Mutation of the conserved base A2451 of 23 S rRNA to U did not abolish the pH dependence of the reaction with puromycin in M. smegmatis, suggesting that A24 51 did not confer the pH dependent role, however, the A 2451U mutation alters the structure of the peptidyl transferase center and changes the pattern of pH-dependent rearrangements, as probed by chemical modification of 23S rRNA.

Mechanism of peptide bond synthesis on the ribosome.

  • Stefan TrobroJ. Åqvist
  • Chemistry, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2005
The observed H-bond network suggests an important structural role of several universally conserved rRNA residues, and the catalytic effect is found to be entirely of entropic origin, in accordance with recent experimental data.

Structural insights into peptide bond formation

The large ribosomal subunit catalyzes peptide bond formation and will do so by using small aminoacyl- and peptidyl-RNA fragments of tRNA. We have refined at 3-Å resolution the structures of both A

Ribosomal peptidyl transferase can withstand mutations at the putative catalytic nucleotide

It is reported that large ribosomal subunits with mutated A2451 showed significant peptidyl transferase activity in several independent assays, and the ribosome apparently promotes transpeptidation not through chemical catalysis, but by properly positioning the substrates of protein synthesis.

Ribosomal crystallography: peptide bond formation and its inhibition.

The rotatory motion is the major component of unified machinery for peptide-bond formation, translocation, and nascent protein progression, since its spiral nature ensures the entrance of the nascent peptide into the ribosomal exit tunnel.

Toward Ribosomal RNA Catalytic Activity in the Absence of Protein

The ease with which alternate catalytic activity was selected from rRNA with a small number of mutations suggests that rRNA may have inherent activity, and represents a step on the path toward isolating that native activity.

The Ribosomal Peptidyl Transferase Center: Structure, Function, Evolution, Inhibition

  • N. PolacekA. Mankin
  • Biology, Chemistry
    Critical reviews in biochemistry and molecular biology
  • 2005
Biochemical, genetic and structural evidence highlight the role of the ribosome as an entropic catalyst that accelerates peptide bond formation primarily by substrate positioning and suggests that peptide release should more strongly depend on chemical catalysis likely involving an rRNA group of the PTC.

Ribosomal crystallography: peptide bond formation, chaperone assistance and antibiotics activity.

  • A. Yonath
  • Biology, Chemistry
    Molecules and cells
  • 2005
Comparisons of high-resolution structures of complexes of antibiotics bound to ribosomes from eubacteria resembling pathogens, to an archaeon that shares properties with eukaryotes and to its mutant that allows antibiotics binding demonstrated the unambiguous difference between mere binding and therapeutical effectiveness.

A structural view on the mechanism of the ribosome-catalyzed peptide bond formation.




A single adenosine with a neutral pKa in the ribosomal peptidyl transferase center.

In vivo mutational analysis of this nucleotide indicates that it has an essential role in ribosomal function, and results are consistent with a mechanism wherein the nucleotide base of A2451 serves as a general acid base during peptide bond formation.

The complete atomic structure of the large ribosomal subunit at 2.4 A resolution.

The crystal structure of the large ribosomal subunit from Haloarcula marismortui is determined at 2.4 angstrom resolution, and it includes 2833 of the subunit's 3045 nucleotides and 27 of its 31 proteins.

Identification of a site on 23S ribosomal RNA located at the peptidyl transferase center.

A model for the functional organization of the peptidyl transferase site involving interaction of domains II and V of 23S rRNA is proposed and from comparative analysis of the 16 available large subunit rRNA sequences, it is proposed that this region of the 23S-like rRNAs is an integral component of the pear-tRNA site.

Possible involvement of Escherichia coli 23S ribosomal RNA in peptide bond formation.

It is demonstrated that an E. coli 23S rRNA transcript synthesized by T7 RNA polymerase in vitro was able to promote peptide bond formation in the presence of 0.5% SDS, and findings strongly suggest that23S r RNA is the peptidyltransferase itself.

23S rRNA similarity from selection for peptidyl transferase mimicry.

Binding of CCdApPuro by a peptidyl transferase-like motif in the absence of protein strengthens the hypothesis that peptidol transfer originated in an RNA world.

X-ray crystal structures of 70S ribosome functional complexes.

Structures of 70S ribosome complexes containing messenger RNA and transfer RNA (tRNA), or tRNA analogs, have been solved by x-ray crystallography at up to 7.8 angstrom resolution. Many details of the

General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme.

The RNA enzyme (ribozyme) from hepatitis delta virus catalyzes self-cleavage of a phosphodiester bond, which expands the catalytic repertoire of RNA and may provide improved rate acceleration.