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Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies

The evolution of enzymes affects how well a species can adapt to new environmental conditions. During enzyme evolution, certain aspects of molecular function are conserved while other aspects can vary. Aspects of function that are more difficult to change or that need to be reused in multiple contex...

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Detalles Bibliográficos
Autores principales: Chiang, Ranyee A., Sali, Andrej, Babbitt, Patricia C.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453236/
https://www.ncbi.nlm.nih.gov/pubmed/18670595
http://dx.doi.org/10.1371/journal.pcbi.1000142
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author Chiang, Ranyee A.
Sali, Andrej
Babbitt, Patricia C.
author_facet Chiang, Ranyee A.
Sali, Andrej
Babbitt, Patricia C.
author_sort Chiang, Ranyee A.
collection PubMed
description The evolution of enzymes affects how well a species can adapt to new environmental conditions. During enzyme evolution, certain aspects of molecular function are conserved while other aspects can vary. Aspects of function that are more difficult to change or that need to be reused in multiple contexts are often conserved, while those that vary may indicate functions that are more easily changed or that are no longer required. In analogy to the study of conservation patterns in enzyme sequences and structures, we have examined the patterns of conservation and variation in enzyme function by analyzing graph isomorphisms among enzyme substrates of a large number of enzyme superfamilies. This systematic analysis of substrate substructures establishes the conservation patterns that typify individual superfamilies. Specifically, we determined the chemical substructures that are conserved among all known substrates of a superfamily and the substructures that are reacting in these substrates and then examined the relationship between the two. Across the 42 superfamilies that were analyzed, substantial variation was found in how much of the conserved substructure is reacting, suggesting that superfamilies may not be easily grouped into discrete and separable categories. Instead, our results suggest that many superfamilies may need to be treated individually for analyses of evolution, function prediction, and guiding enzyme engineering strategies. Annotating superfamilies with these conserved and reacting substructure patterns provides information that is orthogonal to information provided by studies of conservation in superfamily sequences and structures, thereby improving the precision with which we can predict the functions of enzymes of unknown function and direct studies in enzyme engineering. Because the method is automated, it is suitable for large-scale characterization and comparison of fundamental functional capabilities of both characterized and uncharacterized enzyme superfamilies.
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spelling pubmed-24532362008-08-01 Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies Chiang, Ranyee A. Sali, Andrej Babbitt, Patricia C. PLoS Comput Biol Research Article The evolution of enzymes affects how well a species can adapt to new environmental conditions. During enzyme evolution, certain aspects of molecular function are conserved while other aspects can vary. Aspects of function that are more difficult to change or that need to be reused in multiple contexts are often conserved, while those that vary may indicate functions that are more easily changed or that are no longer required. In analogy to the study of conservation patterns in enzyme sequences and structures, we have examined the patterns of conservation and variation in enzyme function by analyzing graph isomorphisms among enzyme substrates of a large number of enzyme superfamilies. This systematic analysis of substrate substructures establishes the conservation patterns that typify individual superfamilies. Specifically, we determined the chemical substructures that are conserved among all known substrates of a superfamily and the substructures that are reacting in these substrates and then examined the relationship between the two. Across the 42 superfamilies that were analyzed, substantial variation was found in how much of the conserved substructure is reacting, suggesting that superfamilies may not be easily grouped into discrete and separable categories. Instead, our results suggest that many superfamilies may need to be treated individually for analyses of evolution, function prediction, and guiding enzyme engineering strategies. Annotating superfamilies with these conserved and reacting substructure patterns provides information that is orthogonal to information provided by studies of conservation in superfamily sequences and structures, thereby improving the precision with which we can predict the functions of enzymes of unknown function and direct studies in enzyme engineering. Because the method is automated, it is suitable for large-scale characterization and comparison of fundamental functional capabilities of both characterized and uncharacterized enzyme superfamilies. Public Library of Science 2008-08-01 /pmc/articles/PMC2453236/ /pubmed/18670595 http://dx.doi.org/10.1371/journal.pcbi.1000142 Text en Chiang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chiang, Ranyee A.
Sali, Andrej
Babbitt, Patricia C.
Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies
title Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies
title_full Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies
title_fullStr Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies
title_full_unstemmed Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies
title_short Evolutionarily Conserved Substrate Substructures for Automated Annotation of Enzyme Superfamilies
title_sort evolutionarily conserved substrate substructures for automated annotation of enzyme superfamilies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453236/
https://www.ncbi.nlm.nih.gov/pubmed/18670595
http://dx.doi.org/10.1371/journal.pcbi.1000142
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