The Structural Basis of Ribosome Activity in Peptide Bond Synthesis
10.1126/science.289.5481.920
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

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 23 S rRNA; there are no protein side-chain atoms closer than about 18 angstroms to the peptide bond being synthesized. The mechanism of peptide bond synthesis appears to resemble the reverse of the acylation step in serine proteases, with the base of A2486 (A2451 in Escherichia coli ) playing the same general base role as histidine-57 in chymotrypsin. The unusual p K a (where K a is the acid dissociation constant) required for A2486 to perform this function may derive in part from its hydrogen bonding to G2482 (G2447 in E. coli ), which also interacts with a buried phosphate that could stabilize unusual tautomers of these two bases. The polypeptide exit tunnel is largely formed by RNA but has significant contributions from proteins L4, L22, and L39e, and its exit is encircled by proteins L19, L22, L23, L24, L29, and L31e.

Bibliography

Nissen, P., Hansen, J., Ban, N., Moore, P. B., & Steitz, T. A. (2000). The Structural Basis of Ribosome Activity in Peptide Bond Synthesis. Science, 289(5481), 920–930.

Authors 5
  1. Poul Nissen (first)
  2. Jeffrey Hansen (additional)
  3. Nenad Ban (additional)
  4. Peter B. Moore (additional)
  5. Thomas A. Steitz (additional)
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Dates
Type When
Created 23 years ago (July 27, 2002, 5:37 a.m.)
Deposited 1 year, 7 months ago (Jan. 13, 2024, 4:18 a.m.)
Indexed 2 weeks, 3 days ago (Aug. 7, 2025, 4:50 p.m.)
Issued 25 years ago (Aug. 11, 2000)
Published 25 years ago (Aug. 11, 2000)
Published Print 25 years ago (Aug. 11, 2000)
Funders 0

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@article{Nissen_2000, title={The Structural Basis of Ribosome Activity in Peptide Bond Synthesis}, volume={289}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.289.5481.920}, DOI={10.1126/science.289.5481.920}, number={5481}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Nissen, Poul and Hansen, Jeffrey and Ban, Nenad and Moore, Peter B. and Steitz, Thomas A.}, year={2000}, month=aug, pages={920–930} }