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Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site

Ribonuclease H1 (RNase H) enzymes are well-conserved endonucleases that are present in all domains of life and are particularly important in the life cycle of retroviruses as domains within reverse transcriptase. Despite extensive study, especially of the E. coli homolog, the interaction of the high...

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Autores principales: Stafford, Kate A., Palmer III, Arthur G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: F1000Research 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032109/
https://www.ncbi.nlm.nih.gov/pubmed/25075292
http://dx.doi.org/10.12688/f1000research.3605.1
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author Stafford, Kate A.
Palmer III, Arthur G.
author_facet Stafford, Kate A.
Palmer III, Arthur G.
author_sort Stafford, Kate A.
collection PubMed
description Ribonuclease H1 (RNase H) enzymes are well-conserved endonucleases that are present in all domains of life and are particularly important in the life cycle of retroviruses as domains within reverse transcriptase. Despite extensive study, especially of the E. coli homolog, the interaction of the highly negatively charged active site with catalytically required magnesium ions remains poorly understood. In this work, we describe molecular dynamics simulations of the E. coli homolog in complex with magnesium ions, as well as simulations of other homologs in their apo states. Collectively, these results suggest that the active site is highly rigid in the apo state of all homologs studied and is conformationally preorganized to favor the binding of a magnesium ion. Notably, representatives of bacterial, eukaryotic, and retroviral RNases H all exhibit similar active-site rigidity, suggesting that this dynamic feature is only subtly modulated by amino acid sequence and is primarily imposed by the distinctive RNase H protein fold.
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spelling pubmed-40321092014-07-28 Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site Stafford, Kate A. Palmer III, Arthur G. F1000Res Research Article Ribonuclease H1 (RNase H) enzymes are well-conserved endonucleases that are present in all domains of life and are particularly important in the life cycle of retroviruses as domains within reverse transcriptase. Despite extensive study, especially of the E. coli homolog, the interaction of the highly negatively charged active site with catalytically required magnesium ions remains poorly understood. In this work, we describe molecular dynamics simulations of the E. coli homolog in complex with magnesium ions, as well as simulations of other homologs in their apo states. Collectively, these results suggest that the active site is highly rigid in the apo state of all homologs studied and is conformationally preorganized to favor the binding of a magnesium ion. Notably, representatives of bacterial, eukaryotic, and retroviral RNases H all exhibit similar active-site rigidity, suggesting that this dynamic feature is only subtly modulated by amino acid sequence and is primarily imposed by the distinctive RNase H protein fold. F1000Research 2014-03-07 /pmc/articles/PMC4032109/ /pubmed/25075292 http://dx.doi.org/10.12688/f1000research.3605.1 Text en Copyright: © 2014 Stafford KA and Palmer III AG http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/publicdomain/zero/1.0/ Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication).
spellingShingle Research Article
Stafford, Kate A.
Palmer III, Arthur G.
Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site
title Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site
title_full Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site
title_fullStr Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site
title_full_unstemmed Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site
title_short Evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease H active site
title_sort evidence from molecular dynamics simulations of conformational preorganization in the ribonuclease h active site
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032109/
https://www.ncbi.nlm.nih.gov/pubmed/25075292
http://dx.doi.org/10.12688/f1000research.3605.1
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