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Mechanism of chiral proofreading during translation of the genetic code
The biological macromolecular world is homochiral and effective enforcement and perpetuation of this homochirality is essential for cell survival. In this study, we present the mechanistic basis of a configuration-specific enzyme that selectively removes D-amino acids erroneously coupled to tRNAs. T...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845328/ https://www.ncbi.nlm.nih.gov/pubmed/24302572 http://dx.doi.org/10.7554/eLife.01519 |
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author | Ahmad, Sadeem Routh, Satya Brata Kamarthapu, Venu Chalissery, Jisha Muthukumar, Sowndarya Hussain, Tanweer Kruparani, Shobha P Deshmukh, Mandar V Sankaranarayanan, Rajan |
author_facet | Ahmad, Sadeem Routh, Satya Brata Kamarthapu, Venu Chalissery, Jisha Muthukumar, Sowndarya Hussain, Tanweer Kruparani, Shobha P Deshmukh, Mandar V Sankaranarayanan, Rajan |
author_sort | Ahmad, Sadeem |
collection | PubMed |
description | The biological macromolecular world is homochiral and effective enforcement and perpetuation of this homochirality is essential for cell survival. In this study, we present the mechanistic basis of a configuration-specific enzyme that selectively removes D-amino acids erroneously coupled to tRNAs. The crystal structure of dimeric D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum in complex with a substrate-mimicking analog shows how it uses an invariant ‘cross-subunit’ Gly-cisPro dipeptide to capture the chiral centre of incoming D-aminoacyl-tRNA. While no protein residues are directly involved in catalysis, the unique side chain-independent mode of substrate recognition provides a clear explanation for DTD’s ability to act on multiple D-amino acids. The strict chiral specificity elegantly explains how the enriched cellular pool of L-aminoacyl-tRNAs escapes this proofreading step. The study thus provides insights into a fundamental enantioselection process and elucidates a chiral enforcement mechanism with a crucial role in preventing D-amino acid infiltration during the evolution of translational apparatus. DOI: http://dx.doi.org/10.7554/eLife.01519.001 |
format | Online Article Text |
id | pubmed-3845328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-38453282013-12-04 Mechanism of chiral proofreading during translation of the genetic code Ahmad, Sadeem Routh, Satya Brata Kamarthapu, Venu Chalissery, Jisha Muthukumar, Sowndarya Hussain, Tanweer Kruparani, Shobha P Deshmukh, Mandar V Sankaranarayanan, Rajan eLife Biochemistry The biological macromolecular world is homochiral and effective enforcement and perpetuation of this homochirality is essential for cell survival. In this study, we present the mechanistic basis of a configuration-specific enzyme that selectively removes D-amino acids erroneously coupled to tRNAs. The crystal structure of dimeric D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum in complex with a substrate-mimicking analog shows how it uses an invariant ‘cross-subunit’ Gly-cisPro dipeptide to capture the chiral centre of incoming D-aminoacyl-tRNA. While no protein residues are directly involved in catalysis, the unique side chain-independent mode of substrate recognition provides a clear explanation for DTD’s ability to act on multiple D-amino acids. The strict chiral specificity elegantly explains how the enriched cellular pool of L-aminoacyl-tRNAs escapes this proofreading step. The study thus provides insights into a fundamental enantioselection process and elucidates a chiral enforcement mechanism with a crucial role in preventing D-amino acid infiltration during the evolution of translational apparatus. DOI: http://dx.doi.org/10.7554/eLife.01519.001 eLife Sciences Publications, Ltd 2013-12-03 /pmc/articles/PMC3845328/ /pubmed/24302572 http://dx.doi.org/10.7554/eLife.01519 Text en Copyright © 2013, Ahmad et al http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry Ahmad, Sadeem Routh, Satya Brata Kamarthapu, Venu Chalissery, Jisha Muthukumar, Sowndarya Hussain, Tanweer Kruparani, Shobha P Deshmukh, Mandar V Sankaranarayanan, Rajan Mechanism of chiral proofreading during translation of the genetic code |
title | Mechanism of chiral proofreading during translation of the genetic code |
title_full | Mechanism of chiral proofreading during translation of the genetic code |
title_fullStr | Mechanism of chiral proofreading during translation of the genetic code |
title_full_unstemmed | Mechanism of chiral proofreading during translation of the genetic code |
title_short | Mechanism of chiral proofreading during translation of the genetic code |
title_sort | mechanism of chiral proofreading during translation of the genetic code |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3845328/ https://www.ncbi.nlm.nih.gov/pubmed/24302572 http://dx.doi.org/10.7554/eLife.01519 |
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